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Dissertations / Theses on the topic 'Biophysics'

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Published: 4 June 2021
Last updated: 28 September 2024

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1

Forrest, Michael. "Biophysics of Purkinje computation." Thesis, University of Warwick, 2008. http://wrap.warwick.ac.uk/84008/.

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Although others have reported and characterised different patterns of Purkinje firing (Womack and Khodakhah, 2002, 2003, 2004; McKay and Turner, 2005) this thesis is the first study that moves beyond their description and investigates the actual basis of their generation. Purkinje cells can intrinsically fire action potentials in a repeating trimodal or bimodal pattern. The trimodal pattern consists of tonic spiking, bursting and quiescence. The bimodal pattern consists of tonic spiking and quiescence. How these firing patterns are generated, and what ascertains which firing pattern is selected, has not been determined to date. We have constructed a detailed biophysical Purkinje cell model that can replicate these patterns and which shows that Na+/K+ pump activity sets the model’s operating mode. We propose that Na+/K+ pump modulation switches the Purkinje cell between different firing modes in a physiological setting and so innovatively hypothesise the Na+/K+ pump to be a computational element in Purkinje information coding. We present supporting in vitro Purkinje cell recordings in the presence of ouabain, which irreversibly blocks the Na+/K+ pump. Climbing fiber (CF) input has been shown experimentally to toggle a Purkinje cell between an up (firing) and down (quiescent) state and set the gain of its response to parallel fiber (PF) input (Mckay et al., 2007). Our Purkinje cell model captures these toggle and gain computations with a novel intracellular calcium computation that we hypothesise to be applicable in real Purkinje cells. So notably, our Purkinje cell model can compute, and importantly, relates biophysics to biological information processing. Our Purkinje cell model is biophysically detailed and as a result is very computationally intensive. This means that, whilst it is appropriate for studying properties of the 8 individual Purkinje cell (e.g. relating channel densities to firing properties), it is unsuitable for incorporation into network simulations. We have overcome this by deploying mathematical transforms to produce a simpler, surrogate version of our model that has the same electrical properties, but a lower computational overhead. Our hope is that this model, of intermediate biological fidelity and medium computational complexity, will be used in the future to bridge cellular and network studies and identify how distinctive Purkinje behaviours are important to network and system function.
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2

Subramaniam, Vinod. "Biophysics of protein misfolding." Enschede : University of Twente [Host], 2007. http://doc.utwente.nl/58042.

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3

Garcia, Gonzalo. "Biophysics of protein interactions." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709387.

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4

Beaulieu-Laroche, Lou. "Dendritic biophysics and evolution." Thesis, Massachusetts Institute of Technology, 2020. https://hdl.handle.net/1721.1/130812.

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Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, February, 2021
Cataloged from the official PDF version of thesis. "February 2021."
Includes bibliographical references (pages 190-207).
The biophysical features of neurons are the building blocks of computation in the brain. Dendrites are the physical site of the vast majority of synaptic connections and can expand the information processing capabilities of neurons. Due to their complex morphological attributes and various ion channels, dendrites shape how thousands of inputs are integrated into behaviorally-relevant outputs at the level of individual neurons. However, several long-standing issues limit our understanding of dendritic biophysics. In addition to distorted electrophysiological measurements, prior studies have largely been limited to ex vivo preparations from rodent animal models, providing little insight for computation in the awake human brain. In this thesis, we overcome these limitations to provide new insights on biophysics at the intersection of dendritic morphology and evolution. In chapter 1, we demonstrate that voltage-clamp analysis, which was employed to derive much of our understanding of synaptic transmission, is incompatible with most synapses because they reside on electrically-compartmentalized spines. We also develop new approaches to provide accurate measurements of synaptic strength. Then, in chapter 2, we directly correlate somatic and distal dendritic activity in the awake mouse visual cortex to show an unexpectedly high degree of coupling in vivo. In chapter 3, we perform dendritic recordings in large human neurons to reveal distinct integrative properties from commonly studied rat neurons. Finally, in chapter 4, we characterize neurons in 10 mammalian species to extract evolutionary rules governing neuronal biophysics and uncover human specializations. Together, these four thesis projects expand our understanding of the influence of dendritic geometry and evolution on neuronal biophysics.
by Lou Beaulieu-Laroche.
Ph. D. in Neuroscience
Ph.D.inNeuroscience Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences
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5

Morrison, Gregory Charles. "Polymer concepts in biophysics." College Park, Md. : University of Maryland, 2008. http://hdl.handle.net/1903/8159.

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Thesis (Ph. D.)--University of Maryland, College Park, 2008.
Thesis research directed by: Dept. of Chemistry and Biochemistry. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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6

Huang, Po-Ssu Rees Douglas C. "Biochemistry and molecular biophysics /." Diss., Pasadena, Calif. : California Institute of Technology, 2004. http://resolver.caltech.edu/CaltechETD:etd-06012004-214823.

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7

Kowalewski, Jacob. "Mathematical Models in Cellular Biophysics." Licentiate thesis, KTH, Applied Physics, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4361.

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Cellular biophysics deals with, among other things, transport processes within cells. This thesis presents two studies where mathematical models have been used to explain how two of these processes occur.

Cellular membranes separate cells from their exterior environment and also divide a cell into several subcellular regions. Since the 1970s lateral diffusion in these membranes has been studied, one the most important experimental techniques in these studies is fluorescence recovery after photobleach (FRAP). A mathematical model developed in this thesis describes how dopamine 1 receptors (D1R) diffuse in a neuronal dendritic membrane. Analytical and numerical methods have been used to solve the partial differential equations that are expressed in the model. The choice of method depends mostly on the complexity of the geometry in the model.

Calcium ions (Ca2+) are known to be involved in several intracellular signaling mechanisms. One interesting concept within this field is a signaling microdomain where the inositol 1,4,5-triphosphate receptor (IP3R) in the endoplasmic reticulum (ER) membrane physically interacts with plasma membrane proteins. This microdomain has been shown to cause the intracellular Ca2+ level to oscillate. The second model in this thesis describes a signaling network involving both ER membrane bound and plasma membrane Ca2+ channels and pumps, among them store-operated Ca2+ (SOC) channels. A MATLAB® toolbox was developed to implement the signaling networks and simulate its properties. This model was also implemented using Virtual cell.

The results show a high resemblance between the mathematical model and FRAP data in the D1R study. The model shows a distinct difference in recovery characteristics of simulated FRAP experiments on whole dendrites and dendritic spines, due to differences in geometry. The model can also explain trapping of D1R in dendritic spines.

The results of the Ca2+ signaling model show that stimulation of IP3R can cause Ca2+ oscillations in the same frequency range as has been seen in experiments. The removing of SOC channels from the model can alter the characteristics as well as qualitative appearance of Ca2+ oscillations.


Cellulär biofysik behandlar bland annat transportprocesser i celler. I denna avhandling presenteras två studier där matematiska modeller har använts för att förklara hur två av dess processer uppkommer.

Cellmembran separerar celler från deras yttre miljö och delar även upp en cell i flera subcellulära regioner. Sedan 1970-talet har lateral diffusion i dessa membran studerats, en av de viktigaste experimentella metoderna i dessa studier är fluorescence recovery after photobleach (FRAP). En matematisk modell utvecklad i denna avhandling beskriver hur dopamin 1-receptorer (D1R) diffunderar i en neural dendrits membran. Analytiska och numeriska metoder har använts för att lösa de partiella differentialekvationer som uttrycks i modellen. Valet av metod beror främst på komplexiteten hos geometrin i modellen.

Kalciumjoner (Ca2+) är kända för att ingå i flera intracellulära signalmekanismer. Ett intressant koncept inom detta fält är en signalerande mikrodomän där inositol 1,4,5-trifosfatreceptorn (IP3R) i endoplasmatiska nätverksmembranet (ER-membranet) fysiskt interagerar med proteiner i plasmamembranet. Denna mikrodomän har visats vara orsak till oscillationer i den intracellulära Ca2+-nivån. Den andra modellen i denna avhandling beskriver ett signalerande nätverk där både Ca2+-kanaler och pumpar bundna i ER-membranet och i plasmamembranet, däribland store-operated Ca2+(SOC)-kanaler, ingår. Ett MATLAB®-verktyg utvecklades för att implementera signalnätverket och simulera dess egenskaper. Denna modell implementerades även i Virtual cell.

Resultaten visar en stark likhet mellan den matematiska modellen och FRAP-datat i D1R-studien. Modellen visar en distinkt skillnad i återhämtningsegenskaper hos simulerade FRAP-experiment på hela dendriter och dendritiska spines, beroende på skillnader i geometri. Modellen kan även förklara infångning av D1R i dendritiska spines.

Resultaten från Ca2+-signaleringmodellen visar att stimulering av IP3R kan orsaka Ca2+-oscillationer inom samma frekvensområde som tidigare setts i experiment. Att ta bort SOC-kanaler från modellen kan ändra karaktär hos, såväl som den kvalitativa uppkomsten av Ca2+-oscillationer.

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8

Gold, Carl Andersen Richard A. Koch Christof. "Biophysics of extracellular action potentials /." Diss., Pasadena, Calif. : California Institute of Technology, 2007. http://resolver.caltech.edu/CaltechETD:etd-05312007-210112.

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9

Testorf, Martin. "Melanophores : cell biophysics and sensor applications /." Linköping : Univ, 2001. http://www.bibl.liu.se/liupubl/disp/disp2001/tek687s.pdf.

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10

Mellor, Ian R. "The biophysics of peptide ion channels." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335759.

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11

Fagone, Paolo. "Modulation of CCTα by membrane biophysics." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398913.

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12

Mukund, Shreyas Ram. "Single molecule biophysics of homologous recombination." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708842.

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13

COLA, FILIPPO. "DYNAMICAL FEEDBACK MODELS IN CELLULAR BIOPHYSICS." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/603836.

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In the present PhD thesis we collected two distinct contributions to the field of mathematical modelling of complex biological phenomena (at the cellular and subcellular level), with the tools of differential equations and spatial stochastic simulations. In the first part we develop a method to determine whether oscillatory temporal signals are a common feature of genetic regulatory networks or they require a fine-tuning of the coupling parameters between nodes of the networks. Modelling a two-nodes genetic network with a system of coupled delay differential equations, we performed a Monte Carlo sampling of the space of parameters of the system, biasing the search in favor of highly oscillating solutions. Estimating with thermodynamic techniques the fraction of the parameters' space associated with oscillations, we conclude that oscillations are indeed a rare feature of these biological control systems. Their dependence on the values of the parameters has been analysed, revealing some simple patterns. In the second part we propose a simple theoretical model for the dynamics of cancer cells subpopulations as observed in experiments in vitro, where a populations of melanoma cells reacts to the depletion of most of its cancer stem cells (a small subpopulation with supposed stem-cells properties and tumorigenic potential) with a large overshoot in the fraction of CSC before returning to homeostatic values. Our model, consisting in a system of delay differential equations, is able to reproduce quite well experimental data and to provide a clear picture of the cellular and molecular details of the control mechanisms, based on experimental evidence and on the emerging paradigm of phenotypic plasticity of cancer cells. A multiscale hybrid-continuum stochastic spatial model on a 2D lattice is also developed to investigate the spatial distribution of cells within the growing tumour, to be verified in immunohistochemistry experiments, with particular regard to CSCs clusterization.
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14

Barley, Jonathan P. "Nonlinear B-Cone Input to the R-G Channel Explains the Abney, Tyndall and Guth Effects." Connect to resource, 1994. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1219337183.

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15

Danial, John Shokri Hanna. "Imaging lipid phase separation in droplet interface bilayers." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:34bb015f-2bc1-43bb-bc29-850e0b55edac.

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The spatiotemporal organization of membrane proteins is implicated in cellular trafficking, signalling and reception. It was proposed that biological membranes partition into lipid rafts that can promote and control the organization of membrane proteins to localize the mentioned processes. Lipid rafts are thought to be transient (microseconds) and small (nanometers), rendering their detection a challenging task. To circumvent this problem, multi-component artificial membrane systems are deployed to study the segregation of lipids at longer time and length scales. In this thesis, multi-component Droplet Interface Bilayers (DIBs) were imaged using fluorescence and interferometric scattering microscopy. DIBs were used to examine and manipulate microscopic lipid domains and to observe, for the first time, transient nanoscopic lipid domains. The techniques and results described here will have important implications on future research in this field.
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16

Cabeza, de Vaca López Israel. "Mapping biophysics through enhanced Monte Carlo techniques." Doctoral thesis, Universitat Politècnica de Catalunya, 2015. http://hdl.handle.net/10803/334172.

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This thesis is focused on the study of molecular interactions at the atomistic detail and is divided into one introductory chapter and four chapters referencing different problems and methodological approaches. All of them are focused on the development and improvement of computational Monte Carlo algorithms to study, in an efficient manner, the behavior of these systems at a classical molecular mechanics level. The four biophysical problems studied in this thesis are: induced fit docking between protein-ligand and between DNA-ligand to understand the binding mechanism, protein stretching response, and generation/ scoring of protein-protein docking poses. The thesis is organized as follows: First chapter corresponds to the state of the art in computational methods to study biophysical interactions, which is the starting point of this thesis. Our in-house PELE algorithm and the main standard methods such as molecular dynamics will be explained in detail. Chapter two is focused on the main PELE modifications to add new features, such as the addition of a new force field, implicit solvent and an anisotropic network specific for DNA simulation studies. We study, compare and validate the conformations generated by six representative DNA fragments with the new PELE features using molecular dynamics as a reference. Chapter three is devoted to applying the new methods implemented and tested in PELE to study protein-ligand interactions and DNA-ligand interactions using four systems. First, we study the porphyrin binding to Gun4 protein combining PELE and molecular dynamics simulations. Besides, we provide a docking pose that has been corroborated by a new crystal structure published during the revision process of the submitted study showing the accuracy of our predictions. In the second project, we use our improved version of PELE to generate the first structural model of an alpha glucose 1,6-bisphosphate substrate bound to the human Phosphomannomutase 2 demonstrating that this ligand can adopt two low-energy orientations. The third project is the study of DNA-ligand interactions for three cisplatin drugs where we evaluate the binding free energy using Markov state models. We show excellent results respect another free energy methods studied with molecular dynamics. The last project is the study of the daunomycin DNA intercalator where we simulate and study the binding process with PELE. Chapter four is focused on the computational study of force extension profiles during the protein unfolding. We added a dynamic harmonic constraint following a similar procedure applied in steered molecular dynamics to our Monte Carlo approach to fix or pull some selected atoms forcing the protein unfolding in a defined direction. We implement and compare with steered molecular dynamics this technique with Ubiquitin and Azurin proteins. Moreover, we add this feature to a well-known algorithm called MCPRO from William Jorgensen¿s group at YALE University to evaluate the free energy associated to the unfolding of the deca-alanine system. Chapter five corresponds to the introduction of a multiscale approach to study protein-protein docking. A coarse-grained model will be combined with a Monte Carlo exploration reducing the degrees of freedom to generate thousands of protein-protein poses in a quick way. Poses produced by this procedure will be refined and ranked through a protonation, hydrogen bond optimization, and minimization protocol at the all-atom representation to identify the best poses. I present two test cases where this procedure has been applied showing a good accuracy in the predictions: tryptogalinin and ferredoxin/flavodoxin systems.
Aquesta tesi es centra en l'estudi de les interaccions moleculars amb detall atomic i es divideix en un capítol d'introducció i quatre capítols que fan referència a diferents problemes i enfocaments metodològics. Tots ells se centren en el desenvolupament i millora dels algoritmes computacionals de Monte Carlo per estudiar, de manera eficient, el comportament d'aquests sistemes a un nivell mecànica molecular clàssica. Els quatre problemes biofísics estudiats en aquesta tesi són: acoblament induït entre la proteïna-lligand i entre DNA-lligant per comprendre el mecanisme d'unió, resposta de les proteïnes a l'estirament, i la generació/puntuació d'acoblament entre poses proteïna-proteïna. La tesi s'organitza de la següent manera: El primer capítol correspon a l'estat de l'art en mètodes computacionals per estudiar les interaccions biofísiques, que és el punt de partida d'aquesta tesi. El nostre PELE algoritme i els principals mètodes estàndard com ara la dinàmica molecular s'explicaran en detall. El capítol dos es centra en les principals modificacions PELE per afegir noves característiques, com ara l'addició d'un nou camp de força, solvent implícit i modes normals per aquests estudis de simulació d'ADN. Es fa un estudi, comparació i validació de les conformacions generades per sis fragments d'ADN representatius amb PELE utilitzant dinàmica molecular com a referència. El tercer capítol està dedicat a l'aplicació dels nous mètodes implementats i provats en PELE per estudiar les interaccions proteïna-lligand i la interacció lligand-DNA utilitzant quatre sistemes. En primer lloc, se estudia la unió a proteïnes GUN4 combinant PELE i simulacions de dinàmica molecular. A més, es proposa un acoblament que ha sigut corroborat per una nova estructura cristal·lina publicada durant el procés de revisió de l'estudi mostrant l'exactitud de les nostres prediccions. En el segon projecte, hem utilitzat la nostra versió millorada de PELE per generar el primer model estructural d'una glucosa alfa substrat 1,6-bisfosfat unit a la fosfomanomutasa humana 2, que demostra que aquest lligant pot adoptar dues orientacions de baiza energia. El tercer projecte és l'estudi de les interaccions d'ADN lligant per tres medicaments cisplatí on se avalua l'energia lliure d'unió utilitzant Markov States Models. Es mostren excel·lents resultats respecte d'altres mètodes d'energia lliure estudiats amb dinàmica molecular. L'últim projecte és l'estudi de l'intercalador d'ADN anomenat daunomicina on es simula i estudia el procés d'unió amb PELE. El capítol 4 es centra en l'estudi computacional dels perfils d'extensió de la força durant el desplegament de la proteïna. Hem afegit una restricció harmònica dinàmica seguint un procediment similar al aplicat en dinàmica molecular en el nostre algoritme Monte Carlo per fixar o moure alguns àtoms seleccionats obligant a desplegar la proteïna en una direcció definida. Aquesta tècnica s'ha implementat i comparat amb dinàmica molecular per les proteïnes ubiquitina i azurin. D'altra banda, hem afegit aquesta modificació a un algoritme ben conegut anomenat MCPRO del grup de William Jorgensen a la Universitat de Yale per avaluar l'energia lliure associada al desplegament del sistema deca alanina. El capítol cinc correspon a la introducció d'un enfocament multiescala per estudiar l'acoblament proteïna-proteïna. Un model de gra gruixut es combinat amb una exploració Monte Carlo per reduir els graus de llibertat i generar milers de poses proteïna-proteïna d'una manera ràpida. Les poses produides per aquest procediment es perfeccionan i evaluan a través d'una protonació, optimització d'enllaços d'hidrogen, i minimització a escala atòmica per identificar les millors poses. Es presenten dos casos de prova on s'ha aplicat aquest procediment que mostra una bona precisió en les prediccions: tryptogalinin i ferredoxina / flavodoxina systems.
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17

Kowalewski, Jacob. "Modeling and Data Analysis in Cellular Biophysics." Doctoral thesis, KTH, Cellens fysik, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-11368.

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Cellular biophysics deals with the physical aspects of cell biology. This thesis presents a number of studies where mathematical models and data analysis can increase our understanding of this field. During recent years development in experimental methods and mathematical modeling have driven the amount of data and complexity in our understanding of cellular biology to a new level. This development has made it possible to describe cellular systems quantitatively where only qualitative descriptions were previously possible. To deal with the complex data and models that arise in this kind of research a combination of tools from physics and cell biology has to be applied; this constitutes a field we call cellular biophysics. The aim of this doctoral thesis is to develop novel approaches in this field. I present eight studies where quantitative modeling and analysis are involved. The first two studies concern cells interacting with their surrounding environment in the kidney. These cells sense fluid flow and respond with calcium (Ca2+) signals. The interaction between fluid and cells in renal tubular epithelium can be described by biomechanical models. This thesis describes a mathematical model of flow sensing by cilia with focus on the flow frequency response and time delay between the mechanical stress and the Ca2+ signaling response. Intracellular Ca2+ is kept at a very low level compared to the extracellular environment, while several intracellular compartments have higher Ca2+ concentration than the cytoplasm. This makes Ca2+ an efficient messenger for intra­cellular signaling, the process whereby signals are transduced from an extracellular stimulus to an intracellular activity such as gene expression. An important type of Ca2+ signaling is oscillations in intracellular Ca2+ concentration which occur due to the concerted interplay between different transport mechanisms within a cell. A study in this thesis examines ways to explain these mechanisms in terms of a mathematical model. Another study in the thesis reports that erythropoietin can regulate the water permeability of astrocytes and that it alters the pattern of Ca2+ oscillations in astrocytes. In this thesis the analysis of this Ca2+ signaling is described. Simulations described in one of the studies show how different geometries can affect the fluorescence recovery and that geometrically constrained reactions can trap diffusing receptors in dendritic spines. When separate time scales are present in a fluorescence revovery after photobleaching (FRAP) experiment the reaction and diffusion components can be studied separately. Applying single particle tracking methods to the migration trajectories of natural killer cells shows that there is a correlation between the formation of conjugates and transient confinement zones (TCZs) in these trajectories in vitro. TCZs are also present in in vivo experiments where they show strong similarities with the in vitro situation. This approach is a novel concept in data analysis methods for tracking immune cells.
Cellens biologiska fysik behandlar de fysikaliska aspekterna av cellbiologi. Denna avhandling presenterar ett antal studier där matematiska modeller och dataanalys kan öka vår förståelse av detta område. Under senare år har utvecklingen av experimentella metoder och matematisk modellering drivit mängden data och komplexiteten i vår förståelse av cellbiologi till en ny nivå. Denna utveckling har gjort det möjligt att beskriva cellulära system kvantitativt där endast kvalitativa beskrivningar tidigare var möjliga. För att hantera de komplexa data och modeller som uppstår i denna typ av forskning krävs en kombination av verktyg från fysik och cellbiologi; detta utgör ett område vi kallar cellens biologiska fysik. Syftet med denna avhandling är att utveckla nya metoder inom detta område. Jag presenterar åtta studier där kvantitativ modellering och analys ingår. De första två studierna behandlar hur celler interagerar med sin omgivning i njurarna. Dessa celler känner av ett vätskeflöde och svarar med kalcium (Ca2+)-signaler. Samspelet mellan vätska och celler i tubulärt njurepitel kan beskrivas med biomekaniska modeller. Denna avhandling beskriver en matematisk modell för flödeskänslighet hos cilier med fokus på flödesfrekvenssvar och tidsfördröjningen mellan den mekaniska påverkan och Ca2+-signaleringssvaret. Intracellulärt Ca2+ hålls på en mycket låg nivå jämfört med den extracellulära miljön, samtidigt som flera intracellulära delar har högre Ca2+-koncentrationen än cytoplasman. Detta gör Ca2+ till en effektiv bärare för intracellulär signalering, den process där signaler överförs från ett extracellulärt stimuli till en intracellulär händelse, exempelvis genuttryck. En viktig typ av Ca2+-signalering är de oscillationer i intracellulär Ca2+-koncentration som uppstår på grund av det ordnade samspelet mellan olika transportmekanismer i en cell. En studie  i denna avhandling undersöker olika sätt att förklara dessa mekanismer i form av en matematisk modell. En annan studie i avhandlingen rapporterar att erytropoietin kan reglera vattenpermeabilitet av astrocyter och att det ändrar mönstret av Ca2+-oscillationer i astrocyter. I denna avhandling beskrivs analysen av denna Ca2+-signalering. Simuleringar som beskrivs i en av studierna visar hur olika geometrier kan påverka fluorescensåterhämtning och att geometriskt begränsade reaktioner kan fånga in receptorer in i dendrittaggar. När separata tidsskalor förekommer i ett fluorescence revovery after photobleaching (FRAP)-experiment kan reaktions- och diffusionskomponenter studeras separat. Tillämpande av single particle tracking-metoder på naturliga mördarceller visar att det finns ett samband mellan bildandet av konjugat och transient confinement zones (TCZs) i dessa trajektorier in vitro. TCZs förekommer också i in vivo-experiment där de visar stora likheter med in vitro-situationen. Denna strategi är ett nytt grepp inom dataanalys-metoder för att spåra immunceller.
QC 20100726
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18

Prokop, Robert M. "Surface thermodynamics and biophysics of the lung." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ28040.pdf.

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19

Karnas, Scott J. "The biophysics of IUdR photon activation therapy." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ58222.pdf.

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20

Hukin, David James John. "Water relations and biophysics of plant cells." Thesis, University of Birmingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.398699.

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21

Katsamba, Panayiota. "Biophysics of helices : devices, bacteria and viruses." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/283006.

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A prevalent morphology in the microscopic world of artificial microswimmers, bacteria and viruses is that of a helix. The intriguingly different physics at play at the small scale level make it necessary for bacteria to employ swimming strategies different from our everyday experience, such as the rotation of a helical filament. Bio-inspired microswimmers that mimic bacterial locomotion achieve propulsion at the microscale level using magnetically actuated, rotating helical filaments. A promising application of these artificial microswimmers is in non-invasive medicine, for drug delivery to tumours or microsurgery. Two crucial features need to be addressed in the design of microswimmers. First, the ability to selectively control large ensembles and second, the adaptivity to move through complex conduit geometries, such as the constrictions and curves of the tortuous tumour microvasculature. In this dissertation, a mechanics-based selective control mechanism for magnetic microswimmers is proposed, and a model and simulation of an elastic helix passing through a constricted microchannel are developed. Thereafter, a theoretical framework is developed for the propulsion by stiff elastic filaments in viscous fluids. In order to address this fluid-structure problem, a pertubative, asymptotic, elastohydrodynamic approach is used to characterise the deformation that arises from and in turn affects the motion. This framework is applied to the helical filaments of bacteria and magnetically actuated microswimmers. The dissertation then turns to the sub-bacterial scale of bacteriophage viruses, 'phages' for short, that infect bacteria by ejecting their genetic material and replicating inside their host. The valuable insight that phages can offer in our fight against pathogenic bacteria and the possibility of phage therapy as an alternative to antibiotics, are of paramount importance to tackle antibiotics resistance. In contrast to typical phages, flagellotropic phages first attach to bacterial flagella, and have the striking ability to reach the cell body for infection, despite their lack of independent motion. The last part of the dissertation develops the first theoretical model for the nut-and-bolt mechanism (proposed by Berg and Anderson in 1973). A nut being rotated will move along a bolt. Similarly, a phage wraps itself around a flagellum possessing helical grooves, and exploits the rotation of the flagellum in order to passively travel along and towards the cell body, according to this mechanism. The predictions from the model agree with experimental observations with respect to directionality, speed and the requirements for succesful translocation.
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22

Schmitt, Jeffrey Daniel. "The biophysics of ion-channel forming peptides." Thesis, University of Bath, 1998. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.760713.

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23

Doktorova, Milka N. "Biophysics of Asymmetric Membranes| Protocols and Revelations." Thesis, Weill Medical College of Cornell University, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10844615.

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Lipid membranes enclose cells and organelles, and actively participate in cellular processes. Their many functional roles require tight regulation of properties including structure and dynamics. Cells achieve this by producing and dynamically tuning the concentration and organization of hundreds of structurally different types of lipid molecules in the various cellular membranes. The cell-bounding plasma membranes of eukaryotes in particular, exhibit an actively maintained asymmetric lipid distribution across their two leaflets. In addition to exposing certain types of lipids to the extracellular space or intracellular milieu, this specialized transbilayer lipid arrangement also affects the properties of the membrane itself and its interactions with proteins, in ways that are difficult to explore and thus not understood. To address this problem and enable further advancements in the field, we have developed both in vitro and in silico protocols for building asymmetric model membranes with finely controlled lipid compositions. These protocols allowed us to investigate the dynamics, energetics and structural consequences of interleaflet communication: with small-angle scattering we uncovered asymmetry-mediated changes in the lipid packing of individual leaflets in free-floating liposomes; with electron spin resonance we revealed the ensuing trends in lipid order; and nuclear magnetic resonance helped us bring new appreciation of the interplay between asymmetric bilayers and transmembrane protein inclusions. To interpret and better understand the experimental observations, we developed a new in silico protocol for constructing atomistic models of tension-free asymmetric bilayers and used it to simulate the experimentally measured membranes and validate the simulation conditions. By devising a novel computational framework for calculating the compressibility of individual bilayer leaflets, we analyzed the energetics of protein interaction with the asymmetric membranes and obtained an estimate of the elastic energy of mixing the two leaflets. Together with additional experimental and computational studies of symmetric membrane systems, the results revealed fascinating ways in which cells can mediate the functional diversity of their membranes. The new methods and protocols leading to these insights generate previously unattainable opportunities for dissecting and exploring membrane-mediated cellular processes.

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Kurganska, M. M. "Clothing biophysics in personal protective equipment use." Thesis, Київський національний університет технологій та дизайну, 2017. https://er.knutd.edu.ua/handle/123456789/7611.

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25

CAO, BAOQIANG. "ON APPLICATIONS OF STATISTICAL LEARNING TO BIOPHYSICS." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1168577852.

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Mirheydari, Mona Sadat. "INVESTIGATION OF THE BIOPHYSICS OF LIPID DROPLETS." Kent State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=kent1498862985023767.

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27

Baez, William David. "RNA Secondary Structures: from Biophysics to Bioinformatics." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1525714439675315.

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28

Akpe, Victor. "Photophysical and Chemical Approaches to Cellular Biophysics." Licentiate thesis, Stockholm : Fysik, Kungliga Tekniska högskolan, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-10097.

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29

Shen, Tongye. "Fluctuations and stochastic dynamics in molecular biophysics /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2002. http://wwwlib.umi.com/cr/ucsd/fullcit?p3061634.

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30

Schwab, David Jason. "Topics in biophysics and disordered quantum systems." Diss., Restricted to subscribing institutions, 2009. http://proquest.umi.com/pqdweb?did=1971489301&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.

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31

Gori, Matteo. "Phase transitions theory and applications to biophysics." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4111.

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Les études et les résultats présentés dans ce manuscrit ont pour but de développer une meilleure compréhension des principes à la base de l'auto-organisation dans les systèmes biologiques. La théorie topologique des transitions de phase est l'un des approches possibles pour fournir une généralisation de la description des transitions de phase dans les systèmes petits ou mésoscopiques. Cette théorie a été rigoureusement enracinée dans deux théorèmes: un contre exemple à l'un de ces théorèmes a été récemment découvert. La première partie de ce manuscrit est donc consacré à mieux comprendre ce «contre-exemple » pour verifier si et comment la théorie peut être sauvé.Dans la deuxieme parte de ce manuscrit les résultats des recherches théoriques, numériques et expérimentales sur la condensation à la Fr "ohlich sont reportés. Ceci est une condition préalable à l'activation des oscillations dipolaires géantes qui entraînent des interactions électrodynamiques à long portée entre les molécules coresonnantes. Dans cette thèse, on montre que les interactions à longue portée affectent sensiblement les propriétés de diffusion des molécules en solution. Une empreinte des interactions à long portée pourrait être un phénomène de «transition» en ce qui concerne le coefficient de diffusion en fonction d'un paramètre de contrôle proportionnel à l’intensité d'interaction. Simulations analogues ont été réalisées afin de valider une approche expérimentale visant à trouver une telle «empreinte» dans les systèmes avec interactions à longue portée
The studies and results reported in this manuscript are aimed to develop a deeper understanding of the principles at the basis of self-organization in biological system.The Topological Theory of phase transitions is one of the possible approaches to provide a generalization of description of phase transitions in small or mesoscopic systems. This theory has been rigorously rooted in two theorems: a counterexample to one of these theorems has been recently found. The first part of this manuscript is devoted to investigation of the "counterexample" to understand if and how the theory can be saved. In the second part of this manuscript the results of theoretical, numerical and experimental investigations on Fr"ohlich-like condensation for normal modes of biomolecules are reported. This is a prerequisite for the activation of giant dipole oscillations in biomolecules which entail long-range electrodynamic interactions between coresonant molecules. In this thesis is shown that long-range interactions markedly affect the self-diffusion properties of molecules in solution. A fingerprint of long-range interactions could be a "transitional" phenomenon concerning the self-diffusion coefficient as a function of a control parameter proportional to interaction strength. Analogous simulations have been performed to validate an experimental approach aimed at finding such "fingerprint" in systems with built-in long-range interactions
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32

Elmlund, Hans. "Protein structure dynamics and interplay : by single-particle electron microscopy." Doctoral thesis, Stockholm : Teknik och hälsa, Technology and Health, Kungliga Tekniska högskolan, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-4669.

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33

Kelly, Ronan. "Biophysics and biochemistry of the pancreatic β-cell." Thesis, University of Oxford, 1989. https://ora.ox.ac.uk/objects/uuid:e815cdec-ad16-4271-84e8-4ec8aaac842e.

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The β-cells of the pancreatic islets of Langerhans are the endocrine cells which secrete the hypoglycaemic hormone insulin. The primary stimulus for insulin secretion is an increase in the plasma glucose concentration, although secretion can be modulated by a variety of hormones and neurotransmitters. The immediate signal for insulin release is calcium entry through the β-cell plasma membrane. Primary secretagogues are glucose and those other secretagogues capable of initiating insulin secretion (e.g. glyceraldehyde, leucine, 2- ketoisokaproate); secondary secretagogues are those which potentiate the effect of glucose but which cannot initiate insulin secretion in the absence of glucose (glucagon, ACh, Forskolin, phorbol esters). Both glucose and the various agents which modulate insulin secretion do so by altering the pattern of B-cell electrical activity, and hence Ca2+ influx. This thesis examines the ionic basis of B-cell electrical activity and the mechanism of its initiation by glucose.
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34

Klingelhoefer, Jochen W. "Biophysics of nanopores-multiscale molecular dynamics simulation studies." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.540136.

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35

Allard, Jun. "Mathematics and biophysics of cortical microtubules in plants." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/30439.

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Microtubules confined to the two-dimensional cortex of elongating plant cells must form a parallel yet dispersed array transverse to the elongation axis for proper cell wall expansion. Collisions between microtubules, which migrate via hybrid treadmilling, can result in plus-end entrainment (zippering) or catastrophe. Here, I present (1) a cell-scale computational model of cortical microtubule organization and (2) a molecular-scale model for microtubule-cortex anchoring and collision-based interactions between microtubules. The first model treats interactions phenomenologically while the second addresses interactions by considering energetic competition between crosslinker binding, microtubule bending and microtubule polymerization. From the cell-scale model, we find that plus-end entrainment leads to self-organization of microtubules into parallel arrays, while collision-induced catastrophe does not. Catastrophe-inducing boundaries can tune the dominant orientation. Changes in dynamic-instability parameters, such as in mor1-1 mutants in Arabidopsis thaliana, can impede self-organization, in agreement with experiment. Increased entrainment, as seen in clasp-1 mutants, conserves self-organization, but delays its onset. Modulating the ability of cell edges to induce catastrophe, as the CLASP protein may do, can tune the dominant direction and regulate organization. The molecular-scale model predicts a higher probability of entrainment at lower collision angles and at longer unanchored lengths of plus-ends. The models lead to several testable predictions, including the effects of reduced microtubule severing in katanin mutants and variable membrane-anchor densities in different plants, including Arabidopsis cells and Tobacco cells.
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36

Eder, Stephan. "Magnetite in organisms and the biophysics underlying magnetoreception." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-161971.

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37

Kerr, Ian Derek. "The biophysics of peptide models of ion channels." Thesis, University of Oxford, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359457.

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38

Ralfs, Arthur C. "Electrically coupled relaxation oscillators with applications to Biophysics /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488194825667224.

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39

Mon, Père Nathaniel. "Statistical biophysics of hematopoiesis and growing cell populations." Doctoral thesis, Universite Libre de Bruxelles, 2020. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/314684.

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Cell populations in the human body form highly complex systems, their behavior driven by countless processes within the cells themselves as well as their interactions with each other and their environment. A mathematical approach to describing their emergent phenomena on the tissue level typically requires abstractions of these underlying systems in order to obtain tractable and interpretable models, which in turn often leads to descriptions involving stochastic processes.In this doctoral thesis two such cellular systems are investigated. The first is the human hematopoietic system: the machinery by which precursor cells of the blood are cultivated and matured in the bone marrow. This process is essential to enable mammalian physiology, from providing oxygen-carrying erythrocytes to ensuring regular upkeep and preservation of the immune system. Obtaining a quantitative understanding of key aspects of this system can provide valuable insights and testable predictions concerning the origin and dynamics of various blood-related diseases, however, in vivo studies of maturing blood cells pose significant challenges and in vitro studies provide only limited predictive power. The system’s hierarchical architecture is on the other hand well fit to the application of mathematical techniques relying only on a few basic assumptions and parameters. This research aims to contribute to two broader questions concerning hematopoiesis, the first being “What is the shape of this system?” and the second “How does it behave?”. Both questions must be answered sufficiently before quantitative models can be developed with enough predictive power to aid in clinical research and applications.The second project stems from questions in oncology concerning the locomotive capabilities of various cancerous cell types, but ultimately poses these in a broader context, attempting to understand cell motion in the context of a growing but spatially restricted population. Drawing from the domain of non-equilibrium statistical mechanics applied to actively moving particles, an important goal is to understand the effects of heightened proliferation on the collective motion.
Les populations cellulaires du corps humain forment des systèmes complexes, leur comportement étant déterminé par d'innombrables processus au sein des cellules elles-mêmes ainsi que par leurs interactions entre elles et avec leur environnement. Une approche mathématique de la description de leurs phénomènes émergents au niveau des tissus nécessite généralement l'abstraction de ces systèmes sous-jacents afin d'obtenir des modèles traitables et interprétables, ce qui à son tour conduit souvent à des descriptions impliquant des processus stochastiques. Dans cette thèse de doctorat, deux de ces systèmes cellulaires sont étudiés.Le premier est le système hématopoïétique humain :la machinerie par laquelle les cellules précurseurs du sang sont cultivées et maturées dans la moelle osseuse. Ce processus est essentiel pour permettre la physiologie des mammifères, depuis la fourniture d'érythrocytes porteurs d'oxygène jusqu'à la préservation du système immunitaire. L'obtention d'une compréhension quantitative des aspects clés de ce système peut fournir des informations précieuses et des prévisions vérifiables concernant l'origine et la dynamique de diverses maladies liées au sang. Cependant, les études in vivo de la maturation des cellules sanguines posent des défis importants, et les études in vitro n'offrent qu'un pouvoir prédictif limité. Par ailleurs, l'architecture hiérarchique du système est bien adaptée à l'application de techniques mathématiques reposant uniquement sur quelques hypothèses et paramètres. Cette recherche vise à contribuer à deux questions plus larges concernant l'hématopoïèse, la première étant "Quelle est la forme de ce système" et la seconde "Comment se comporte-t-il ?Ces deux questions doivent recevoir une réponse suffisante avant que des modèles quantitatifs puissent être développés avec un pouvoir prédictif suffisant pour faciliter la recherche clinique et les applications.Le deuxième projet découle de questions en oncologie concernant les capacités locomotrices de divers types de cellules cancéreuses, mais les pose finalement dans un contexte plus large, en essayant de comprendre le mouvement des cellules dans le disposition d'une population croissante mais limitée dans l'espace. En s'appuyant sur le domaine de la mécanique statistique du non-équilibre appliquée aux particules en mouvement actif, un objectif important est de comprendre les effets d'une prolifération accrue sur le mouvement collectif.
Celpopulaties in het menselijk lichaam vormen complexe systemen. Het individuele celgedrag wordt gedreven door zowel talloze processen binnenin de cellen zelf, als door interacties met elkaar en hun omgeving. Een wiskundige beschrijving van fenomenen op het niveau van de weefsels vereist abstracties van deze onderliggende systemen om hanteerbare en interpreteerbare modellen te verkrijgen, waarbij vaak stochastische processen betrokken zijn. In dit proefschrift worden twee van dergelijke cellulaire systemen onderzocht. Het eerste is het menselijke hematopoëtische systeem: de machinerie waarmee voorlopercellen van het bloed worden ontwikkeld in het beenmerg. Dit proces is essentieel om de fysiologie van zoogdieren mogelijk te maken, van het leveren van zuurstofdragende rode bloedcellen tot het onderhoud van het immuunsysteem. Het verkrijgen van een kwantitatief inzicht in aspecten van dit systeem kan waardevolle inzichten en testbare voorspellingen opleveren met betrekking tot de oorsprong en de dynamiek van verschillende bloedgerelateerde ziekten. Echter, in vivo studies van ontwikkelende bloedcellen vormen een aanzienlijke uitdaging en in vitro studies leveren slechts een beperkt voorspellend vermogen op. De hiërarchische architectuur van het systeem verleent zich daarentegen handig naar het toepassen van wiskundige technieken op basis van slechts enkele aannames en parameters. Dit onderzoek heeft als doel bij te dragen aan twee bredere vragen met betrekking tot hematopoëse, de eerste zijnde "Wat is de structuur van dit systeem?" en de tweede "Hoe gedraagt het zich?". Beide vragen moeten voldoende worden beantwoord voordat kwantitatieve modellen kunnen worden ontwikkeld met voldoende voorspellende kracht om klinisch onderzoek te kunnen bijstaan.Het tweede project komt voort uit vraagstukken in de oncologie over de motorische capaciteiten van verschillende kankerceltypes, maar plaatst deze uiteindelijk in een bredere context, waarbij getracht wordt de stochastische beweging van cellen te begrijpen in de context van een groeiende maar ruimtelijk beperkte populatie. Uitgaande van het domein van de niet-evenwicht statistische mechanica toegepast op actief bewegende deeltjes, is een belangrijk doel het begrijpen van de effecten van een verhoogde proliferatie op de collectieve beweging.
Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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40

Carson, Jo. "Spider Speculations: A Physics and Biophysics of Storytelling." Digital Commons @ East Tennessee State University, 2008. http://amzn.com/1559362839.

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"Jo Carson lays bare her personal investigation into her own creative process after a spider bite on her back begins a series of life-altering events. Spider Speculations applies cutting edge mind-body science, quantum physics and ancient shamanistic techniques to describe how stories work in our bodies and our lives, and what happens when real stories are used in a public way. Carson, whose ability to capture the spoken word hallmarks her community-based work, sets down this story in her own distinctive voice, interspersing the journey with examples of her performance work. This truly original American book will speak to anyone thinking about art and community or engaging with people's stories"--Publisher description.
https://dc.etsu.edu/alumni_books/1019/thumbnail.jpg
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41

Mammano, Fabio. "Biophysics of the Cochlea. Theory, Experiments and Applications." Doctoral thesis, SISSA, 1992. http://hdl.handle.net/20.500.11767/4438.

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This work attempts to bring together theoretical and experimental aspects of cochlear biophysics. In both cases, the focus is on the relationship between the motility of outer hair cells and the filtering properties of the basilar membrane, as this seems the key for understanding the functioning of the peripheral auditory system. From the theoretical side, the hydrodynamics of the cochlea is studied in detail. A possible mechanism for coupling the outer hair cells to the mechanics of the basilar membrane is proposed and analysed mathematically. From the experimental side, the effects of stimulating the cochlea with extracellular current are investigated by means of laser interferometry. The necessary apparatus and the software for data acquisition were engineered in the course of this investigation. A rapid return in the realm of mathematical modelling concludes this work, with an eye on possible applications of physiological knowledge to speech recognition. The newcomer is given a succint introduction to the cochlear world in Chapter 1. A new model of cochlear biomechanics is presented in Chapter 2. A set of experiments aiming at clarifying the role of outer hair cell motility in the control of the vibration pattern of the basilar membrane are described in Chapter 3. The role of active cochlear mechanics in the processing of speech is explored in Chapter 4. Chapters 2 and 4 are the result of an intense collaboration with Prof. Renato Nobili at the Department of Physics of Padova University, Italy, following a preparatory period with Prof. Campbell L. Searle at the Massachusetts Institute of Technology, Boston, U .S.A. The results of Chapter 3 were obtained thanks to the expertise of Dr. Jonathan Ashmore, in his laboratory at the Department of Physiology of Bristol University, England.
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42

Danielsson, Emma. "Towards a better understanding of protein structures : assessing the sulfur bridge in Cystine through photofragmentation." Thesis, Uppsala universitet, Materialteori, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-416437.

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This work aims to investigate the fragmentation of an ionized Cystine molecule, as simulated in the framework of molecular dynamics and quantum mechanics. Cystine is viewed as a model system for larger sets of peptides -- ultimately contributing to the understanding of protein photofragmentation, which is crucial for determining the structure of a protein using new methods. The analysis software was written in Python, partly in conjunction with another student. The photofragmentation of the molecule is analyzed in terms of bond integrity versus time and mass-to-charge ratios for the resulting fragments. Generally, the molecule disintegrates into more and smaller fragments the higher the degree of ionization is.
I det föreliggande arbetet undersöks fragmenteringen av en joniserad molekyl Cystin, som simulerats medelst molekyldynamik och kvantmekanik. Cystin betraktas som ett modellsystem för större peptidstrukturer -- något som i längden kan bidra till större förståelse för fotofragmentering av proteiner, vilket i sin tur är avgörande inom nya metoder för strukturbestämning. Analysprogrammet skrevs i Python och delvis i samarbete med en annan student. Molekylens fotofragmentering analyseras med avseende på bindningsintegritet över tid, samt mass-laddningskvot hos de resulterande fragmenten. I allmänhet sönderfaller molekylen till fler och mindre fragment ju högre joniseringsnivån är.
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43

Faigle, Christoph. "The Optical Stretcher." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-202092.

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The mechanical parameters of biological cells are relevant indicators of their function or of disease. For example, certain cancerous cells are more deformable than healthy cells. The challenge consists in developing methods that can measure these parameters while not affecting the cell. The Optical Stretcher is a microfluidic system that deforms single suspended cells without contact using lasers and determines the cells’ viscoelastic properties. The advantage compared to standard methods of molecular biology is that cells do not need to be treated with additional markers. Basic versions of the Optical Stretcher have existed for some years. These allow the measurement of homogeneous cell populations. Up until now, it was only possible to calculate average population values of compliance. To characterize inhomogeneous populations however, it is necessary to consider each single cell and measure additional mechanical or optical parameters such as the refractive index. This work highlights various extensions of the Optical Stretcher. A novel procedure, including an improved image processing algorithm, is presented to analyze mechanical data in real time. In combination with measurements of the optical refractive index, single cells can now be characterized in more detail. Moreover, it is now possible to extract interesting subpopulations that can be further examined with molecular biology techniques. Depending on the intended purpose, novel devices for cell measurements, based on microfluidic and optical considerations, are presented. The fundamental concept involves microstructured chips that can be integrated into a commercial microscope. These chips offer the possibility of separating measured cell populations according to their mechanical properties. This separation, including mathematical classification, is demonstrated. These methods are tested with cell types of differing mechanical properties to prove their applicability in practice. Single cells are sorted into their respective population of origin. These novel methods offer the possibility of a versatile device to be applied in biophysical research.
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44

Durell, Stewart Richard. "Biophysical studies of plastocyanin /." The Ohio State University, 1989. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487673114114086.

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45

King, Paul M. "Application of free energy perturbation calculations to molecular biophysics." Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.257951.

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46

Burton, B. G. "Visual ecology, biophysics and the adaptability of fly photoreceptors." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597151.

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I examine whether it is possible for the temporal resolution and reliability of a photoreceptor to vary across the eye. This possibility has not been addressed before in any animal and yet it is important for our understanding of how visual systems may be designed to register patterns of optic flow or to track moving targets. In the male blowfly, Calliphora vicina, I show that both spatial and temporal acuity are higher at the front of the eye and fall off with retinal eccentricity. The particular pattern of tuning observed emphasises the importance of tracking to the male fly, a behaviour commonly observed in flies prior to mating. To investigate this possibility further, in Chapter 3 I compare the responses of male and female photoreceptors to simulated target stimuli. For this purpose I use the housefly, Musca domestica, a species whose anatomical and behavioural sex-differences are well documented. The male photoreceptor responds much more powerfully to small moving targets than the female and response amplitude greatly exceeds that predicted from conventional models of photoreceptors dynamics. In particular, the male photoreceptor boosts the signals generated by targets moving within the behavioural regime of distances and speeds. These results allow the limits of male pursuit vision to be determined and demonstrate the impact of behaviour on retinal function. Adaptation of photoreceptor sensitivity and temporal resolution to ambient illumination is a well-known phenomenon. This process is usually considered to be complete within seconds. However, I show in M. domestica that significant improvements in temporal resolution and reliability can occur over a much longer period. These improvements are derived from a more consistent registration of the timing of photon absorption events and appear to be associated with a reduction in rhabdomeral surface area.
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47

Du, Chao. "Stochastic Modeling and Bayesian Inference with Applications in Biophysics." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10366.

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This thesis explores stochastic modeling and Bayesian inference strategies in the context of the following three problems: 1) Modeling the complex interactions between and within molecules; 2) Extracting information from stepwise signals that are commonly found in biophysical experiments; 3) Improving the computational efficiency of a non-parametric Bayesian inference algorithm. Chapter 1 studies the data from a recent single-molecule biophysical experiment on enzyme kinetics. Using a stochastic network model, we analyze the autocorrelation of experimental fluorescence intensity and the autocorrelation of enzymatic reaction times. This chapter shows that the stochastic network model is capable of explaining the experimental data in depth and further explains why the enzyme molecules behave fundamentally differently from what the classical model predicts. The modern knowledge on the molecular kinetics is often learned through the information extracted from stepwise signals in experiments utilizing fluorescence spectroscopy. Chapter 2 proposes a new Bayesian method to estimate the change-points in stepwise signals. This approach utilizes marginal likelihood as the tool of inference. This chapter illustrates the impact of the choice of prior on the estimator and provides guidelines for setting the prior. Based on the results of simulation study, this method outperforms several existing change-points estimators under certain settings. Furthermore, DNA array CGH data and single molecule data are analyzed with this approach. Chapter 3 focuses on the optional Polya tree, a newly established non-parametric Bayesian approach (Wong and Li 2010). While the existing study shows that the optional Polya tree is promising in analyzing high dimensional data, its applications are hindered by the high computational costs. A heuristic algorithm is proposed in this chapter, with an attempt to speed up the optional Polya tree inference. This study demonstrates that the new algorithm can reduce the running time significantly with a negligible loss of precision.
Statistics
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48

Le, Tung T. "Single-molecule biophysics of DNA bending: looping and unlooping." Diss., Georgia Institute of Technology, 2015. http://hdl.handle.net/1853/53979.

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DNA bending plays a vital role in numerous cellular activities such as transcription, viral packaging, and nucleosome formation. Therefore, understanding the physics of DNA bending at the length scales relevant to these processes is one of the main keys to the quantitative description of life. However, previous studies provide a divided picture on how DNA should be modeled in strong bending condition relevant to biology. My thesis is devoted to answering how far an elastic rod model can be applied to DNA. We consider several subtle features that could potentially lead to the break-down of the worm-like chain model, such as local bendedness of the sequence and large bending angles. We used single-molecule Fluorescence Resonance Energy Transfer to track looping and unlooping of single DNA molecules in real time. We compared the measured looping and unlooping rates with theoretical predictions of the worm-like chain model. We found that the intrinsic curvature of the sequence affects the looping propensity of short DNA and an extended worm-like chain model including the helical parameters of individual base pairs could adequately explain our measurements. For DNA with random sequence and negligible curvature, we discovered that the worm-like chain model could explain the stability of small DNA loops only down to a critical loop size. Below the critical loop size, the bending stress stored in the DNA loop became less sensitive to loop size, indicative of softened dsDNA. The critical loop size is sensitive to salt condition, especially to magnesium at mM concentrations. This finding enabled us to explain several contrasting results in the past and shed new light on the energetics of DNA bending.
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49

Koussa, Mounir Ahmad. "The Biophysics of Vertebrate Hearing: A Single-Molecule Approach." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17467499.

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Inner-ear mechanotransduction relies on tip links, fine protein filaments made of cadherin-23 and protocadherin-15 that convey tension to mechanosensitive channels at the tips of hair-cell stereocilia. The tip-link cadherins are thought to form a heterotetrameric complex, with two cadherin-23 molecules forming the upper part of the filament and two protocadherin-15 molecules forming the lower end. The interaction between cadherin-23 and protocadherin-15 is mediated by their N-terminal tips. Missense mutations that modify the interaction interface impair binding and lead to deafness. We have developed molecular tools to perform single-molecule force spectroscopy on the tip-link bond. Self-assembling DNA nanoswitches are functionalized with the interacting tips of cadherin-23 and protocadherin-15 using the enzyme sortase under conditions that preserve protein function. These tip-link-functionalized nanoswitches are designed to provide a signature force-extension profile, which allows us to identify single-molecule rupture events that result from applying force. Using this system, we have been able to measure the cadherin-23-protocadherin-15 single-molecule force-dependent off rate, as well as the concentration-dependent on rate for a single pair of these proteins. The rates suggest that a single bond is inadequate to withstand physiological forces for physiological times, but we construct a new model for tip-link dynamics which greatly alters our understanding of tip-link function and explains the necessity for a two-filament tip link.
Medical Sciences
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50

Norton, Stephen R. "Linear dichroism spectroscopy and biophysics of an amyloid protein." Thesis, University of Warwick, 2015. http://wrap.warwick.ac.uk/79946/.

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Though Parkinson’s Disease is known to be caused by cell death in one region of the brain, and though the protein α-synuclein is known to be associated with it, the causes are still poorly understood. It has not yet been shown how α-synuclein may cause cells to die, with research focusing on the range of structures the protein is able to adopt. The classic amyloid fibrils are currently believed to be non-toxic, but smaller, soluble oligomers appear to be the toxic species. Key to toxicity and to the normal function of α-synucein (also unknown to-date) appear to be the ability of the protein to bind to lipids, as toxicity may be due to oligomers forming pores in cells, and the normal function of the protein may be in vesicle transport. The work presented in this thesis represents a collection of studies, across several disciplines, that test aspects of the behaviour of α-synuclein. Circular dichroism and fluorescence data presented here show that the protein interacts with the lipid POPS in a concentration-dependent manner. Linear dichroism was an important and complementary technique to these, but required some method refinement and sample preparation improvement. This work is presented in this thesis, alongside experimental and theoretical studies into the behaviour of lipid vesicles in Couette flow. It was shown that certain lipids perform better in Couette flow, particularly the mixture of POPC and POPS. This informed the linear dichroism studies, and enabled experiments suggesting that oligomers of α-synuclein may insert across the membrane of vesicles. If confirmed, this would support the amyloid pore theory of α-synuclein toxicity.
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