Journal articles: 'Mechanics and kinetics of myosin motors'

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Nayak, Arnab, Tianbang Wang, Peter Franz, Walter Steffen, Igor Chizhov, Georgios Tsiavaliaris, and Mamta Amrute-Nayak. "Single-molecule analysis reveals that regulatory light chains fine-tune skeletal myosin II function." Journal of Biological Chemistry 295, no. 20 (April 9, 2020): 7046–59. http://dx.doi.org/10.1074/jbc.ra120.012774.

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Myosin II is the main force-generating motor during muscle contraction. Myosin II exists as different isoforms that are involved in diverse physiological functions. One outstanding question is whether the myosin heavy chain (MHC) isoforms alone account for these distinct physiological properties. Unique sets of essential and regulatory light chains (RLCs) are known to assemble with specific MHCs, raising the intriguing possibility that light chains contribute to specialized myosin functions. Here, we asked whether different RLCs contribute to this functional diversification. To this end, we generated chimeric motors by reconstituting the MHC fast isoform (MyHC-IId) and slow isoform (MHC-I) with different light-chain variants. As a result of the RLC swapping, actin filament sliding velocity increased by ∼10-fold for the slow myosin and decreased by >3-fold for the fast myosin. Results from ensemble molecule solution kinetics and single-molecule optical trapping measurements provided in-depth insights into altered chemo-mechanical properties of the myosin motors that affect the sliding speed. Notably, we found that the mechanical output of both slow and fast myosins is sensitive to the RLC isoform. We therefore propose that RLCs are crucial for fine-tuning the myosin function.

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Greenberg, Michael J., Tianming Lin, Henry Shuman, and E. Michael Ostap. "Mechanochemical tuning of myosin-I by the N-terminal region." Proceedings of the National Academy of Sciences 112, no. 26 (June 8, 2015): E3337—E3344. http://dx.doi.org/10.1073/pnas.1506633112.

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Myosins are molecular motors that generate force to power a wide array of motile cellular functions. Myosins have the inherent ability to change their ATPase kinetics and force-generating properties when they encounter mechanical loads; however, little is known about the structural elements in myosin responsible for force sensing. Recent structural and biophysical studies have shown that myosin-I isoforms, Myosin-Ib (Myo1b) and Myosin-Ic (Myo1c), have similar unloaded kinetics and sequences but substantially different responses to forces that resist their working strokes. Myo1b has the properties of a tension-sensing anchor, slowing its actin-detachment kinetics by two orders of magnitude with just 1 pN of resisting force, whereas Myo1c has the properties of a slow transporter, generating power without slowing under 1-pN loads that would stall Myo1b. To examine the structural elements that lead to differences in force sensing, we used single-molecule and ensemble kinetic techniques to show that the myosin-I N-terminal region (NTR) plays a critical role in tuning myosin-I mechanochemistry. We found that replacing the Myo1c NTR with the Myo1b NTR changes the identity of the primary force-sensitive transition of Myo1c, resulting in sensitivity to forces of <2 pN. Additionally, we found that the NTR plays an important role in stabilizing the post–power-stroke conformation. These results identify the NTR as an important structural element in myosin force sensing and suggest a mechanism for generating diversity of function among myosin isoforms.

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Littlefield, Kimberly Palmiter, Douglas M. Swank, Becky M. Sanchez, Aileen F. Knowles, David M. Warshaw, and Sanford I. Bernstein. "The converter domain modulates kinetic properties ofDrosophila myosin." American Journal of Physiology-Cell Physiology 284, no. 4 (April 1, 2003): C1031—C1038. http://dx.doi.org/10.1152/ajpcell.00474.2002.

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Recently the converter domain, an integral part of the “mechanical element” common to all molecular motors, was proposed to modulate the kinetic properties of Drosophila chimeric myosin isoforms. Here we investigated the molecular basis of actin filament velocity ( V actin) changes previously observed with the chimeric EMB-IC and IFI-EC myosin proteins [the embryonic body wall muscle (EMB) and indirect flight muscle isoforms (IFI) with genetic substitution of the IFI and EMB converter domains, respectively]. In the laser trap assay the IFI and IFI-EC myosins generate the same unitary step displacement (IFI = 7.3 ± 1.0 nm, IFI-EC = 5.8 ± 0.9 nm; means ± SE). Thus converter-mediated differences in the kinetics of strong actin-myosin binding, rather than the mechanical capabilities of the protein, must account for the observed V actin values. Basal and actin-activated ATPase assays and skinned fiber mechanical experiments definitively support a role for the converter domain in modulating the kinetic properties of the myosin protein. We propose that the converter domain kinetically couples the Pi and ADP release steps that occur during the cross-bridge cycle.

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Lecarpentier, Edouard R., Victor A. Claes, Oumar Timbely, Abdelilah Arsalane, Jacques A. Wipff, Jean-Louis M. Hébert, Francine Y. Michel, and Yves C. Lecarpentier. "Mechanics and energetics of myosin molecular motors from nonpregnant human myometrium." Journal of Applied Physiology 111, no. 4 (October 2011): 1096–105. http://dx.doi.org/10.1152/japplphysiol.00414.2011.

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Mechanical properties of spontaneously contracting isolated nonpregnant human myometrium (NPHM) were investigated throughout the whole continuum of load from zero load up to isometry. This made it possible to assess the three-dimensional tension-velocity-length (T-V-L) relationship characterizing the level of contractility and to determine crossbridge (CB) kinetics of myosin molecular motors. Seventy-seven muscle strips were obtained from hysterectomy in 42 nonpregnant patients. Contraction and relaxation parameters were measured during spontaneous mechanical activity. The isotonic tension-peak velocity (T-V) relationship was hyperbolic in 30 cases and nonhyperbolic in 47 cases. When the T-V relationship was hyperbolic, the Huxley formalism could be used to calculate CB kinetics and CB unitary force. At the whole muscle level and for a given isotonic load level, part of the V-L phase plane showed a common pathway, so that a given instantaneous length corresponded to only one possible instantaneous velocity, independent of time and initial length. At the molecular level, rate constants for CB attachment and detachment were dramatically low, ∼100 times lower than those of striated muscles, and ∼5 to 10 times lower than those of other smooth muscles. The CB unitary force was ∼1.4 ± 0.1 pN. NPHM shared similar basic contractile properties with striated muscles, reflected in the three-dimensional T-V-L relationship characterizing the contractile level. Low CB attachment and detachment rate constants made it possible to generate normal CB unitary force and normal muscle tension in NPHM, even though it contracted extremely slowly compared with other muscles.

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Marcucci, Lorenzo, Hiroki Fukunaga, Toshio Yanagida, and Mitsuhiro Iwaki. "The Synergic Role of Actomyosin Architecture and Biased Detachment in Muscle Energetics: Insights in Cross Bridge Mechanism beyond the Lever-Arm Swing." International Journal of Molecular Sciences 22, no. 13 (June 29, 2021): 7037. http://dx.doi.org/10.3390/ijms22137037.

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Muscle energetics reflects the ability of myosin motors to convert chemical energy into mechanical energy. How this process takes place remains one of the most elusive questions in the field. Here, we combined experimental measurements of in vitro sliding velocity based on DNA-origami built filaments carrying myosins with different lever arm length and Monte Carlo simulations based on a model which accounts for three basic components: (i) the geometrical hindrance, (ii) the mechano-sensing mechanism, and (iii) the biased kinetics for stretched or compressed motors. The model simulations showed that the geometrical hindrance due to acto-myosin spatial mismatching and the preferential detachment of compressed motors are synergic in generating the rapid increase in the ATP-ase rate from isometric to moderate velocities of contraction, thus acting as an energy-conservation strategy in muscle contraction. The velocity measurements on a DNA-origami filament that preserves the motors’ distribution showed that geometrical hindrance and biased detachment generate a non-zero sliding velocity even without rotation of the myosin lever-arm, which is widely recognized as the basic event in muscle contraction. Because biased detachment is a mechanism for the rectification of thermal fluctuations, in the Brownian-ratchet framework, we predict that it requires a non-negligible amount of energy to preserve the second law of thermodynamics. Taken together, our theoretical and experimental results elucidate less considered components in the chemo-mechanical energy transduction in muscle.

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Vargiu, Romina, Anna Perinu, Antonello De Lisa, Frank Tintrup, Francesco Manca, and Rino Mancinelli. "Origin of Motion in the Human Ureter: Mechanics, Energetics and Kinetics of the Myosin Molecular Motors." Urologia Journal 79, no. 2 (April 2012): 123–29. http://dx.doi.org/10.5301/ru.2012.9110.

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Background Ureteral peristalsis is the result of coordinated mechanical motor performance of longitudinal and circular smooth muscle layer of the ureter wall. The main aim of this study was to characterize in smooth muscle of proximal segments of human ureter, the mechanical properties at level of muscle tissue and at level of myosin molecular motors. Methods Ureteral samples were collected from 15 patients, who underwent nephrectomy for renal cancer. Smooth muscle strips longitudinally and circularly oriented from proximal segments of human ureter were used for the in vitro experiments. Mechanical indices including the maximum unloaded shortening velocity (Vmax), and the maximum isometric tension (P0) normalized per cross-sectional area, were determined in vitro determined in electrically evoked contractions of longitudinal and circular smooth muscle strips. Myosin cross-bridge (CB) number per mm2 (Ψ) the elementary force per single CB (Ψ) and kinetic parameters were calculated in muscle strips, using Huxley's equations adapted to nonsarcomeric muscles. Results Longitudinal smooth muscle strips exhibited a significantly (p<0.05) faster Vmax (63%) and a higher P0 (40%), if compared to circular strips. Moreover, longitudinal muscle strips showed a significantly higher unitary force (Ψ) per CB. However, no significant differences were observed in CB number, the attachment (f1) and the detachment (g2) rate constants between longitudinal and circular muscle strips. Conclusions The main result obtained in the present work documents that the mechanical, energetic and unitary forces per CB of longitudinal layer of proximal ureter are better compared to the circular one; these preliminary findings suggested, unlike intestinal smooth muscle, a major role of longitudinal smooth muscle layer in the ureter peristalsis.

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Lecarpentier, Yves. "Mechanical and Thermodynamic Properties of Mesenchymal Stem Cells Differentiated into Myofibroblasts: A Commentary on the Article “Statistical Mechanics of Non-Muscle Myosin IIA in Human Bone Marrow-Derived Mesenchymal Stromal Cells Seeded in a Collagen Scaffold: A Thermodynamic Near-Equilibrium Linear System Modified by the Tripeptide Arg-Gly-Asp (RGD)”." Journal of Stem Cells Research, Development & Therapy 7, no. 3 (September 10, 2021): 1–4. http://dx.doi.org/10.24966/srdt-2060/100075.

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Mesenchymal Stem Cells (MSCs) are multipotent stromal cells found in bone marrow and have the capacity to differentiate into myofibroblast. In contractile myofibroblasts, the molecular motor is the non-muscle myosin (NMIIA) which differs from the muscle myosin by its ultra-slow kinetics. The differentiation of MSCs into myofibroblasts is promoted by the “Transforming Growth Factor” (TGF-b) which represents a potentially target against tissue fibrosis and cancer.

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Seow, Chun Y. "Hill’s equation of muscle performance and its hidden insight on molecular mechanisms." Journal of General Physiology 142, no. 6 (November 25, 2013): 561–73. http://dx.doi.org/10.1085/jgp.201311107.

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Muscles shorten faster against light loads than they do against heavy loads. The hyperbolic equation first used by A.V. Hill over seven decades ago to illustrate the relationship between shortening velocity and load is still the predominant method used to characterize muscle performance, even though it has been regarded as purely empirical and lacking precision in predicting velocities at high and low loads. Popularity of the Hill equation has been sustained perhaps because of historical reasons, but its simplicity is certainly attractive. The descriptive nature of the equation does not diminish its role as a useful tool in our quest to understand animal locomotion and optimal design of muscle-powered devices like bicycles. In this Review, an analysis is presented to illustrate the connection between the historic Hill equation and the kinetics of myosin cross-bridge cycle based on the latest findings on myosin motor interaction with actin filaments within the structural confines of a sarcomere. In light of the new data and perspective, some previous studies of force–velocity relations of muscle are revisited to further our understanding of muscle mechanics and the underlying biochemical events, specifically how extracellular and intracellular environment, protein isoform expression, and posttranslational modification of contractile and regulatory proteins change the interaction between myosin and actin that in turn alter muscle force, shortening velocity, and the relationship between them.

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Lecarpentier, Yves, Vincent Kindler, Xénophon Krokidis, Marie-Luce Bochaton-Piallat, Victor Claes, Jean-Louis Hébert, Alexandre Vallée, and Olivier Schussler. "Statistical Mechanics of Non-Muscle Myosin IIA in Human Bone Marrow-Derived Mesenchymal Stromal Cells Seeded in a Collagen Scaffold: A Thermodynamic Near-Equilibrium Linear System Modified by the Tripeptide Arg-Gly-Asp (RGD)." Cells 9, no. 6 (June 21, 2020): 1510. http://dx.doi.org/10.3390/cells9061510.

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Mesenchymal stromal cells (MSCs) were obtained from human bone marrow and amplified in cultures supplemented with human platelet lysate. Once semi-confluent, cells were seeded in solid collagen scaffolds that were rapidly colonized by the cells generating a 3D cell scaffold. Here, they acquired a myofibroblast phenotype and when exposed to appropriate chemical stimulus, developed tension and cell shortening, similar to those of striated and smooth muscle cells. Myofibroblasts contained a molecular motor—the non-muscle myosin type IIA (NMMIIA) whose crossbridge (CB) kinetics are dramatically slow compared with striated and smooth muscle myosins. Huxley’s equations were used to determine the molecular mechanical properties of NMMIIA. Thank to the great number of NMMIIA molecules, we determined the statistical mechanics (SM) of MSCs, using the grand canonical ensemble which made it possible to calculate various thermodynamic entities such as the chemical affinity, statistical entropy, internal energy, thermodynamic flow, thermodynamic force, and entropy production rate. The linear relationship observed between the thermodynamic force and the thermodynamic flow allowed to establish that MSC-laden in collagen scaffolds were in a near-equilibrium stationary state (affinity ≪ RT), MSCs were also seeded in solid collagen scaffolds functionalized with the tripeptide Arg-Gly-Asp (RGD). This induced major changes in NMMIIA SM particularly by increasing the rate of entropy production. In conclusion, collagen scaffolds laden with MSCs can be viewed as a non-muscle contractile bioengineered tissue operating in a near-equilibrium linear regime, whose SM could be substantially modified by the RGD peptide.

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Holmes, K. C., D. R. Trentham, R. Simmons, H. Lee Sweeney, and Anne Houdusse. "The motor mechanism of myosin V: insights for muscle contraction." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 359, no. 1452 (December 29, 2004): 1829–42. http://dx.doi.org/10.1098/rstb.2004.1576.

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It is 50 years since the sliding of actin and myosin filaments was proposed as the basis of force generation and shortening in striated muscle. Although this is now generally accepted, the detailed molecular mechanism of how myosin uses adenosine triphosphate to generate force during its cyclic interaction with actin is only now being unravelled. New insights have come from the unconventional myosins, especially myosin V. Myosin V is kinetically tuned to allow movement on actin filaments as a single molecule, which has led to new kinetic, mechanical and structural data that have filled in missing pieces of the actomyosin–chemo–mechanical transduction puzzle.

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Ciocanel, Maria-Veronica, Aravind Chandrasekaran, Carli Mager, Qin Ni, Garegin A. Papoian, and Adriana Dawes. "Simulated actin reorganization mediated by motor proteins." PLOS Computational Biology 18, no. 4 (April 7, 2022): e1010026. http://dx.doi.org/10.1371/journal.pcbi.1010026.

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Cortical actin networks are highly dynamic and play critical roles in shaping the mechanical properties of cells. The actin cytoskeleton undergoes significant reorganization in many different contexts, including during directed cell migration and over the course of the cell cycle, when cortical actin can transition between different configurations such as open patched meshworks, homogeneous distributions, and aligned bundles. Several types of myosin motor proteins, characterized by different kinetic parameters, have been involved in this reorganization of actin filaments. Given the limitations in studying the interactions of actin with myosin in vivo, we propose stochastic agent-based models and develop a set of data analysis measures to assess how myosin motor proteins mediate various actin organizations. In particular, we identify individual motor parameters, such as motor binding rate and step size, that generate actin networks with different levels of contractility and different patterns of myosin motor localization, which have previously been observed experimentally. In simulations where two motor populations with distinct kinetic parameters interact with the same actin network, we find that motors may act in a complementary way, by tuning the actin network organization, or in an antagonistic way, where one motor emerges as dominant. This modeling and data analysis framework also uncovers parameter regimes where spatial segregation between motor populations is achieved. By allowing for changes in kinetic rates during the actin-myosin dynamic simulations, our work suggests that certain actin-myosin organizations may require additional regulation beyond mediation by motor proteins in order to reconfigure the cytoskeleton network on experimentally-observed timescales.

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Ito, Kohji, Mitsuo Ikebe, Taku Kashiyama, Toshifumi Mogami, Takahide Kon, and Keiichi Yamamoto. "1P303 Kinetic mechanism of the Fastest Motor Protein, Chara Myosin(9. Molecular motor (I),Poster Session,Abstract,Meeting Program of EABS & BSJ 2006)." Seibutsu Butsuri 46, supplement2 (2006): S222. http://dx.doi.org/10.2142/biophys.46.s222_3.

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Xie, Ping, Shuo-Xing Dou, and Peng-Ye Wang. "Model for kinetics of myosin-V molecular motors." Biophysical Chemistry 120, no. 3 (April 2006): 225–36. http://dx.doi.org/10.1016/j.bpc.2005.11.008.

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Lecarpentier, Yves, Victor Claes, Jean-Louis Hébert, Olivier Schussler, and Alexandre Vallée. "Mechanical and Thermodynamic Properties of Non-Muscle Contractile Tissues: The Myofibroblast and the Molecular Motor Non-Muscle Myosin Type IIA." International Journal of Molecular Sciences 22, no. 14 (July 20, 2021): 7738. http://dx.doi.org/10.3390/ijms22147738.

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Myofibroblasts are contractile cells found in multiple tissues. They are physiological cells as in the human placenta and can be obtained from bone marrow mesenchymal stem cells after differentiation by transforming growth factor-β (TGF-β). They are also found in the stroma of cancerous tissues and can be located in non-muscle contractile tissues. When stimulated by an electric current or after exposure to KCl, these tissues contract. They relax either by lowering the intracellular Ca2+ concentration (by means of isosorbide dinitrate or sildenafil) or by inhibiting actin-myosin interactions (by means of 2,3-butanedione monoxime or blebbistatin). Their shortening velocity and their developed tension are dramatically low compared to those of muscles. Like sarcomeric and smooth muscles, they obey Frank-Starling’s law and exhibit the Hill hyperbolic tension-velocity relationship. The molecular motor of the myofibroblast is the non-muscle myosin type IIA (NMIIA). Its essential characteristic is the extreme slowness of its molecular kinetics. In contrast, NMIIA develops a unitary force similar to that of muscle myosins. From a thermodynamic point of view, non-muscle contractile tissues containing NMIIA operate extremely close to equilibrium in a linear stationary mode.

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Gunther, Laura K., John A. Rohde, Wanjian Tang, Joseph A. Cirilo, Christopher P. Marang, Brent D. Scott, David D. Thomas, Edward P. Debold, and Christopher M. Yengo. "FRET and optical trapping reveal mechanisms of actin activation of the power stroke and phosphate release in myosin V." Journal of Biological Chemistry 295, no. 51 (October 14, 2020): 17383–97. http://dx.doi.org/10.1074/jbc.ra120.015632.

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Myosins generate force and motion by precisely coordinating their mechanical and chemical cycles, but the nature and timing of this coordination remains controversial. We utilized a FRET approach to examine the kinetics of structural changes in the force-generating lever arm in myosin V. We directly compared the FRET results with single-molecule mechanical events examined by optical trapping. We introduced a mutation (S217A) in the conserved switch I region of the active site to examine how myosin couples structural changes in the actin- and nucleotide-binding regions with force generation. Specifically, S217A enhanced the maximum rate of lever arm priming (recovery stroke) while slowing ATP hydrolysis, demonstrating that it uncouples these two steps. We determined that the mutation dramatically slows both actin-induced rotation of the lever arm (power stroke) and phosphate release (≥10-fold), whereas our simulations suggest that the maximum rate of both steps is unchanged by the mutation. Time-resolved FRET revealed that the structure of the pre– and post–power stroke conformations and mole fractions of these conformations were not altered by the mutation. Optical trapping results demonstrated that S217A does not dramatically alter unitary displacements or slow the working stroke rate constant, consistent with the mutation disrupting an actin-induced conformational change prior to the power stroke. We propose that communication between the actin- and nucleotide-binding regions of myosin assures a proper actin-binding interface and active site have formed before producing a power stroke. Variability in this coupling is likely crucial for mediating motor-based functions such as muscle contraction and intracellular transport.

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Hilbert, Lennart. "Modeling Coordinated Kinetics in Large Groups of Muscle Myosin Motors." Biophysical Journal 110, no. 3 (February 2016): 7a. http://dx.doi.org/10.1016/j.bpj.2015.11.090.

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Sellers, James R., John Kendrick-Jones, and Claudia Veigel. "Single Molecule Mechanics Of Myosin Motors Under Load." Biophysical Journal 96, no. 3 (February 2009): 553a. http://dx.doi.org/10.1016/j.bpj.2008.12.3636.

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Schilstra, Maria J., and Stephen R. Martin. "An elastically tethered viscous load imposes a regular gait on the motion of myosin-V. Simulation of the effect of transient force relaxation on a stochastic process." Journal of The Royal Society Interface 3, no. 6 (October 31, 2005): 153–65. http://dx.doi.org/10.1098/rsif.2005.0098.

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Myosin-V is a processive molecular motor that moves membrane vesicles along actin tracks. In the simple model for motor and cargo motion investigated here, an elastic connection between motor and cargo transiently absorbs the abrupt mechanical transitions of the motor, and allows smooth relaxation of the cargo to a new position. We use a stochastic description to model motor stepping, with kinetics that depends on the instantaneous force exerted on the motor through the elastic connection. Tether relaxation is modelled as a continuous process, in which the rate is determined by the viscous drag of the cargo and the stiffness profile of the connection. Quantitative combined stochastic–continuous simulation of the dynamics of this system shows that bulky loads can impose a highly regular gait on the motor. If the characteristics of the elastic connection are similar to those of the myosin-II coiled-coil domain, the myosin-V motor, tether and cargo form a true escapement, in which the motor only escapes from its current position after one or more force thresholds have been crossed. Multiple thresholds limit the variation in tether length to values below that of the total step size.

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Caremani, Marco, and Massimo Reconditi. "Anisotropic Elasticity of the Myosin Motor in Muscle." International Journal of Molecular Sciences 23, no. 5 (February 25, 2022): 2566. http://dx.doi.org/10.3390/ijms23052566.

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To define the mechanics and energetics of the myosin motor action in muscles, it is mandatory to know fundamental parameters such as the stiffness and the force of the single myosin motor, and the fraction of motors attached during contraction. These parameters can be defined in situ using sarcomere−level mechanics in single muscle fibers under the assumption that the stiffness of a myosin dimer with both motors attached (as occurs in rigor, when all motors are attached) is twice that of a single motor (as occurs in the isometric contraction). We use a mechanical/structural model to identify the constraints that underpin the stiffness of the myosin dimer with both motors attached to actin. By comparing the results of the model with the data in the literature, we conclude that the two-fold axial stiffness of the dimers with both motors attached is justified by a stiffness of the myosin motor that is anisotropic and higher along the axis of the myofilaments. A lower azimuthal stiffness of the motor plays an important role in the complex architecture of the sarcomere by allowing the motors to attach to actin filaments at different azimuthal angles relative to the thick filament.

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Lecarpentier, Y., F. X. Blanc, J. Quillard, J. L. Hébert, X. Krokidis, and C. Coirault. "Statistical mechanics of myosin molecular motors in skeletal muscles." Journal of Theoretical Biology 235, no. 3 (August 2005): 381–92. http://dx.doi.org/10.1016/j.jtbi.2005.01.018.

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Franz, Peter, Wiebke Ewert, Matthias Preller, and Georgios Tsiavaliaris. "Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and Pi Release." International Journal of Molecular Sciences 22, no. 1 (December 24, 2020): 104. http://dx.doi.org/10.3390/ijms22010104.

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The actomyosin system generates mechanical work with the execution of the power stroke, an ATP-driven, two-step rotational swing of the myosin-neck that occurs post ATP hydrolysis during the transition from weakly to strongly actin-bound myosin states concomitant with Pi release and prior to ADP dissociation. The activating role of actin on product release and force generation is well documented; however, the communication paths associated with weak-to-strong transitions are poorly characterized. With the aid of mutant analyses based on kinetic investigations and simulations, we identified the W-helix as an important hub coupling the structural changes of switch elements during ATP hydrolysis to temporally controlled interactions with actin that are passed to the central transducer and converter. Disturbing the W-helix/transducer pathway increased actin-activated ATP turnover and reduced motor performance as a consequence of prolonged duration of the strongly actin-attached states. Actin-triggered Pi release was accelerated, while ADP release considerably decelerated, both limiting maximum ATPase, thus transforming myosin-2 into a high-duty-ratio motor. This kinetic signature of the mutant allowed us to define the fractional occupancies of intermediate states during the ATPase cycle providing evidence that myosin populates a cleft-closure state of strong actin interaction during the weak-to-strong transition with bound hydrolysis products before accomplishing the power stroke.

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Dasbiswas, Kinjal, Shiqiong Hu, Alexander D. Bershadsky, and Samuel A. Safran. "Registry Kinetics of Myosin Motor Stacks Driven by Mechanical Force-Induced Actin Turnover." Biophysical Journal 117, no. 5 (September 2019): 856–66. http://dx.doi.org/10.1016/j.bpj.2019.07.040.

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Baker, Josh E. "Saturation of Actin-Myosin Kinetics and Mechanics." Biophysical Journal 120, no. 3 (February 2021): 60a. http://dx.doi.org/10.1016/j.bpj.2020.11.596.

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Hsu, Hsiu-Hao, Ming-Jer Huang, Pei-Hsi Chou, Yen-Po Huang, Hsin-Chieh Chen, and You-Li Chou. "THE BIOMECHANICAL ANALYSIS OF MYOSIN V IN MULTIPLE-PATHS MODEL." Biomedical Engineering: Applications, Basis and Communications 21, no. 02 (April 2009): 89–95. http://dx.doi.org/10.4015/s1016237209001179.

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Myosin V, a two-headed motor protein, moves along actin filaments toward the positive end. Similar to other molecular motors, myosin V hydrolyzes Adenosine tri-phosphate (ATP) and releases its product to produce movement. This study proposes a multiple-paths model that considers the hydrolysis processes of catalytic sites at the two heads of myosin V as independent. The proposed model describes the myosin V transition process by seven states, with one load-dependent transition rate among these states. This model demonstrates how myosin V steps forward at different chemical reaction paths. This study also uses the enzyme kinetics to calculate the mean velocity. Stochastic processes are used to analyze the randomness as well. Analytical results reveal that the theoretical mean velocities, mean movement lengths, and randomness with various ATP concentrations under external load agree with the experimental data.

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Linari, M., G. Piazzesi, and V. Lombardi. "The Effect of Myofilament Compliance on Kinetics of Force Generation by Myosin Motors in Muscle." Biophysical Journal 96, no. 2 (January 2009): 583–92. http://dx.doi.org/10.1016/j.bpj.2008.09.026.

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Gunther, Laura K., John A. Rohde, Wanjian Tang, Shane D. Walton, William C. Unrath, Darshan V. Trivedi, Joseph M. Muretta, David D. Thomas, and Christopher M. Yengo. "Converter domain mutations in myosin alter structural kinetics and motor function." Journal of Biological Chemistry 294, no. 5 (December 5, 2018): 1554–67. http://dx.doi.org/10.1074/jbc.ra118.006128.

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Myosins are molecular motors that use a conserved ATPase cycle to generate force. We investigated two mutations in the converter domain of myosin V (R712G and F750L) to examine how altering specific structural transitions in the motor ATPase cycle can impair myosin mechanochemistry. The corresponding mutations in the human β-cardiac myosin gene are associated with hypertrophic and dilated cardiomyopathy, respectively. Despite similar steady-state actin-activated ATPase and unloaded in vitro motility–sliding velocities, both R712G and F750L were less able to overcome frictional loads measured in the loaded motility assay. Transient kinetic analysis and stopped-flow FRET demonstrated that the R712G mutation slowed the maximum ATP hydrolysis and recovery-stroke rate constants, whereas the F750L mutation enhanced these steps. In both mutants, the fast and slow power-stroke as well as actin-activated phosphate release rate constants were not significantly different from WT. Time-resolved FRET experiments revealed that R712G and F750L populate the pre- and post-power–stroke states with similar FRET distance and distance distribution profiles. The R712G mutant increased the mole fraction in the post-power–stroke conformation in the strong actin-binding states, whereas the F750L decreased this population in the actomyosin ADP state. We conclude that mutations in key allosteric pathways can shift the equilibrium and/or alter the activation energy associated with key structural transitions without altering the overall conformation of the pre- and post-power–stroke states. Thus, therapies designed to alter the transition between structural states may be able to rescue the impaired motor function induced by disease mutations.

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Bueno, Carlos, James Liman, Nicholas P. Schafer, Margaret S. Cheung, and Peter G. Wolynes. "A generalized Flory-Stockmayer kinetic theory of connectivity percolation and rigidity percolation of cytoskeletal networks." PLOS Computational Biology 18, no. 5 (May 9, 2022): e1010105. http://dx.doi.org/10.1371/journal.pcbi.1010105.

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Actin networks are essential for living cells to move, reproduce, and sense their environments. The dynamic and rheological behavior of actin networks is modulated by actin-binding proteins such as α-actinin, Arp2/3, and myosin. There is experimental evidence that actin-binding proteins modulate the cooperation of myosin motors by connecting the actin network. In this work, we present an analytical mean field model, using the Flory-Stockmayer theory of gelation, to understand how different actin-binding proteins change the connectivity of the actin filaments as the networks are formed. We follow the kinetics of the networks and estimate the concentrations of actin-binding proteins that are needed to reach connectivity percolation as well as to reach rigidity percolation. We find that Arp2/3 increases the actomyosin connectivity in the network in a non-monotonic way. We also describe how changing the connectivity of actomyosin networks modulates the ability of motors to exert forces, leading to three possible phases of the networks with distinctive dynamical characteristics: a sol phase, a gel phase, and an active phase. Thus, changes in the concentration and activity of actin-binding proteins in cells lead to a phase transition of the actin network, allowing the cells to perform active contraction and change their rheological properties.

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Greene, Peter R. "Effects of Thermal Tension Transients on the Muscle Crossbridge." Biophysical Reviews and Letters 11, no. 03 (September 2016): 117–26. http://dx.doi.org/10.1142/s1793048016500053.

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The transverse thermal fluctuations of the myosin molecule are significant. This paper explores the contribution of lateral myosin bending to the developed crossbridge force and power stroke. The equipartition theorem is used to calculate the mode amplitudes for myosin bending. Crossbridge axial force [Formula: see text] and power stroke [Formula: see text] are developed by transverse in-plane fluctuations along the [Formula: see text]- and [Formula: see text]-axes. Practical applications include the effects of temperature on the flexibility of the myosin molecule stiffness and tension, relevant to man-made fabrication of synthetic muscle using micromachines and nanowires. Scaling laws for the [Formula: see text] bending amplitude depend on filament length, mode number, and stiffness, as [Formula: see text], and (EI)[Formula: see text]. This paper quantifies the effects of thermal motion on the mechanics of miniature molecular motors, including the muscle crossbridge.

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Oguchi, Yusuke, Sergey V. Mikhailenko, Takashi Ohki, Adrian O. Olivares, Enrique M. De La Cruz, and Shin'ichi Ishiwata. "2P132 Angular dependence of ADP dissociation kinetics in myosin V under directional loading(Molecular motors,Oral Presentations)." Seibutsu Butsuri 47, supplement (2007): S146. http://dx.doi.org/10.2142/biophys.47.s146_1.

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Lee, Stacey, and Sanjay Kumar. "Actomyosin stress fiber mechanosensing in 2D and 3D." F1000Research 5 (September 7, 2016): 2261. http://dx.doi.org/10.12688/f1000research.8800.1.

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Mechanotransduction is the process through which cells survey the mechanical properties of their environment, convert these mechanical inputs into biochemical signals, and modulate their phenotype in response. These mechanical inputs, which may be encoded in the form of extracellular matrix stiffness, dimensionality, and adhesion, all strongly influence cell morphology, migration, and fate decisions. One mechanism through which cells on planar or pseudo-planar matrices exert tensile forces and interrogate microenvironmental mechanics is through stress fibers, which are bundles composed of actin filaments and, in most cases, non-muscle myosin II filaments. Stress fibers form a continuous structural network that is mechanically coupled to the extracellular matrix through focal adhesions. Furthermore, myosin-driven contractility plays a central role in the ability of stress fibers to sense matrix mechanics and generate tension. Here, we review the distinct roles that non-muscle myosin II plays in driving mechanosensing and focus specifically on motility. In a closely related discussion, we also describe stress fiber classification schemes and the differing roles of various myosin isoforms in each category. Finally, we briefly highlight recent studies exploring mechanosensing in three-dimensional environments, in which matrix content, structure, and mechanics are often tightly interrelated. Stress fibers and the myosin motors therein represent an intriguing and functionally important biological system in which mechanics, biochemistry, and architecture all converge.

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Lecarpentier, Yves, Victor Claes, Édouard Lecarpentier, François-Xavier Blanc, Thierry Joseph, Bart Geraets, Xénophon Krokidis, and Jean-Louis Hébert. "Comparative statistical mechanics of myosin molecular motors in rat heart, diaphragm and tracheal smooth muscle." Comptes Rendus Biologies 334, no. 10 (October 2011): 725–36. http://dx.doi.org/10.1016/j.crvi.2011.08.001.

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Picariello, Hannah S., Rajappa S. Kenchappa, Vandana Rai, James F. Crish, Athanassios Dovas, Katarzyna Pogoda, Mariah McMahon, et al. "Myosin IIA suppresses glioblastoma development in a mechanically sensitive manner." Proceedings of the National Academy of Sciences 116, no. 31 (June 24, 2019): 15550–59. http://dx.doi.org/10.1073/pnas.1902847116.

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The ability of glioblastoma to disperse through the brain contributes to its lethality, and blocking this behavior has been an appealing therapeutic approach. Although a number of proinvasive signaling pathways are active in glioblastoma, many are redundant, so targeting one can be overcome by activating another. However, these pathways converge on nonredundant components of the cytoskeleton, and we have shown that inhibiting one of these—the myosin II family of cytoskeletal motors—blocks glioblastoma invasion even with simultaneous activation of multiple upstream promigratory pathways. Myosin IIA and IIB are the most prevalent isoforms of myosin II in glioblastoma, and we now show that codeleting these myosins markedly impairs tumorigenesis and significantly prolongs survival in a rodent model of this disease. However, while targeting just myosin IIA also impairs tumor invasion, it surprisingly increases tumor proliferation in a manner that depends on environmental mechanics. On soft surfaces myosin IIA deletion enhances ERK1/2 activity, while on stiff surfaces it enhances the activity of NFκB, not only in glioblastoma but in triple-negative breast carcinoma and normal keratinocytes as well. We conclude myosin IIA suppresses tumorigenesis in at least two ways that are modulated by the mechanics of the tumor and its stroma. Our results also suggest that inhibiting tumor invasion can enhance tumor proliferation and that effective therapy requires targeting cellular components that drive both proliferation and invasion simultaneously.

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Debold, E. P., S. E. Beck, and D. M. Warshaw. "Effect of low pH on single skeletal muscle myosin mechanics and kinetics." American Journal of Physiology-Cell Physiology 295, no. 1 (July 2008): C173—C179. http://dx.doi.org/10.1152/ajpcell.00172.2008.

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Acidosis (low pH) is the oldest putative agent of muscular fatigue, but the molecular mechanism underlying its depressive effect on muscular performance remains unresolved. Therefore, the effect of low pH on the molecular mechanics and kinetics of chicken skeletal muscle myosin was studied using in vitro motility (IVM) and single molecule laser trap assays. Decreasing pH from 7.4 to 6.4 at saturating ATP slowed actin filament velocity ( Vactin) in the IVM by 36%. Single molecule experiments, at 1 μM ATP, decreased the average unitary step size of myosin ( d) from 10 ± 2 nm (pH 7.4) to 2 ± 1 nm (pH 6.4). Individual binding events at low pH were consistent with the presence of a population of both productive (average d = 10 nm) and nonproductive (average d = 0 nm) actomyosin interactions. Raising the ATP concentration from 1 μM to 1 mM at pH 6.4 restored d (9 ± 3 nm), suggesting that the lifetime of the nonproductive interactions is solely dependent on the [ATP]. Vactin, however, was not restored by raising the [ATP] (1–10 mM) in the IVM assay, suggesting that low pH also prolongs actin strong binding ( ton). Measurement of ton as a function of the [ATP] in the single molecule assay suggested that acidosis prolongs ton by slowing the rate of ADP release. Thus, in a detachment limited model of motility (i.e., Vactin ∼ d/ ton), a slowed rate of ADP release and the presence of nonproductive actomyosin interactions could account for the acidosis-induced decrease in Vactin, suggesting a molecular explanation for this component of muscular fatigue.

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Greenberg, Michael J., James D. Watt, Michelle Jones, Katarzyna Kazmierczak, Danuta Szczesna-Cordary, and Jeffrey R. Moore. "Regulatory light chain mutations associated with cardiomyopathy affect myosin mechanics and kinetics." Journal of Molecular and Cellular Cardiology 46, no. 1 (January 2009): 108–15. http://dx.doi.org/10.1016/j.yjmcc.2008.09.126.

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Greenberg, Michael J., Tanya R. Mealy, Michelle Jones, Danuta Szczesna-Cordary, and Jeffrey R. Moore. "The Molecular Effects of Skeletal Muscle Fatigue on Myosin Mechanics and Kinetics." Biophysical Journal 96, no. 3 (February 2009): 496a. http://dx.doi.org/10.1016/j.bpj.2008.12.2561.

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Nelson, Shane R., Kathleen M. Trybus, and David M. Warshaw. "Liposome Transport by Myosin Va Motors: Coupling Through Lipid Membranes Modulates Cooperative Motor Interactions and Mechanics." Biophysical Journal 100, no. 3 (February 2011): 118a. http://dx.doi.org/10.1016/j.bpj.2010.12.854.

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Månsson, Alf. "Hypothesis: Single Actomyosin Properties Account for Ensemble Behavior in Active Muscle Shortening and Isometric Contraction." International Journal of Molecular Sciences 21, no. 21 (November 9, 2020): 8399. http://dx.doi.org/10.3390/ijms21218399.

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Muscle contraction results from cyclic interactions between myosin II motors and actin with two sets of proteins organized in overlapping thick and thin filaments, respectively, in a nearly crystalline lattice in a muscle sarcomere. However, a sarcomere contains a huge number of other proteins, some with important roles in muscle contraction. In particular, these include thin filament proteins, troponin and tropomyosin; thick filament proteins, myosin binding protein C; and the elastic protein, titin, that connects the thin and thick filaments. Furthermore, the order and 3D organization of the myofilament lattice may be important per se for contractile function. It is possible to model muscle contraction based on actin and myosin alone with properties derived in studies using single molecules and biochemical solution kinetics. It is also possible to reproduce several features of muscle contraction in experiments using only isolated actin and myosin, arguing against the importance of order and accessory proteins. Therefore, in this paper, it is hypothesized that “single molecule actomyosin properties account for the contractile properties of a half sarcomere during shortening and isometric contraction at almost saturating Ca concentrations”. In this paper, existing evidence for and against this hypothesis is reviewed and new modeling results to support the arguments are presented. Finally, further experimental tests are proposed, which if they corroborate, at least approximately, the hypothesis, should significantly benefit future effective analysis of a range of experimental studies, as well as drug discovery efforts.

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Laplaud, Valentin, Nicolas Levernier, Judith Pineau, Mabel San Roman, Lucie Barbier, Pablo J. Sáez, Ana-Maria Lennon-Duménil, et al. "Pinching the cortex of live cells reveals thickness instabilities caused by myosin II motors." Science Advances 7, no. 27 (July 2021): eabe3640. http://dx.doi.org/10.1126/sciadv.abe3640.

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The cell cortex is a contractile actin meshwork, which determines cell shape and is essential for cell mechanics, migration, and division. Because its thickness is below optical resolution, there is a tendency to consider the cortex as a thin uniform two-dimensional layer. Using two mutually attracted magnetic beads, one inside the cell and the other in the extracellular medium, we pinch the cortex of dendritic cells and provide an accurate and time-resolved measure of its thickness. Our observations draw a new picture of the cell cortex as a highly dynamic layer, harboring large fluctuations in its third dimension because of actomyosin contractility. We propose that the cortex dynamics might be responsible for the fast shape-changing capacity of highly contractile cells that use amoeboid-like migration.

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39

Hellstrand, Per. "Cross-bridge kinetics and shortening in smooth muscle." Canadian Journal of Physiology and Pharmacology 72, no. 11 (November 1, 1994): 1334–37. http://dx.doi.org/10.1139/y94-192.

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Stiffness measurements were performed on smooth muscle preparations from guinea-pig taenia coli to obtain information on the number of attached cross bridges under varying contractile conditions. The normalized stiffness of the cross-bridge system in smooth muscle may be of a magnitude similar to that assumed in skeletal muscle. Transition from isometric contraction to unloaded shortening was associated with a decrease in stiffness to 50% or less of the isometric value, slightly higher than that found in skeletal muscle fibers. Comparison of phasic (5 s) and tonic (5 min) contractions showed lower Vmax, intracellular [Ca2+], and myosin 20 kDa light chain phosphorylation at 5 min, indicating development of a latch state. Isometric force and stiffness were identical in the two types of contraction. However, stiffness during unloaded shortening was greater in the latch state, which may be the result of the presence of a population of cross bridges with a low rate constant for detachment.Key words: smooth muscle mechanics, cross bridges, latch, myosin phosphorylation.

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Shirakawa, I., K. Oiwa, S. Chaen, T. Shimizu, H. Tanaka, and H. Sugi. "The mode of ATP-dependent microtubule-kinesin sliding in the auxotonic condition." Journal of Experimental Biology 198, no. 8 (August 1, 1995): 1809–15. http://dx.doi.org/10.1242/jeb.198.8.1809.

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Kinesin is a motor protein that converts chemical energy derived from ATP hydrolysis into mechanical work to transport cellular components along microtubules. We studied the properties of ATP-dependent microtubule-kinesin sliding with two different in vitro assay systems. In one assay system, a kinesin-coated glass microneedle (elastic coefficient, 1-2.5 pN microns -1) was made to slide along an axoneme. Using this system, we obtained the relationship between the force (= load) on the microneedle and the velocity of microneedle-kinesin sliding in the auxotonic condition, in which the load on the microtubule-kinesin contacts increased as sliding progressed. The force-velocity curve was upwardly convex (maximum velocity Vmax, 0.58 +/- 0.15 microns s-1; maximum isometric force P0, 5.0 +/- 1.6 pN) and was similar to that of in vitro actin-myosin sliding in the auxotonic condition, suggesting that the two motor protein systems have fundamental kinetic properties in common. In the other assay system, an axoneme attached to a glass microneedle (elastic coefficient, 4-5 pN microns -1) was made to slide on a kinesin-coated glass surface (Vmax, 0.68 +/- 0.17 microns s-1; P0, 46.1 +/- 18.6 pN). The change in shape of the axoneme indicated an enormous flexibility of randomly oriented kinesin molecules.

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Descovich, Carlos Patino, Daniel B. Cortes, Sean Ryan, Jazmine Nash, Li Zhang, Paul S. Maddox, Francois Nedelec, and Amy Shaub Maddox. "Cross-linkers both drive and brake cytoskeletal remodeling and furrowing in cytokinesis." Molecular Biology of the Cell 29, no. 5 (March 2018): 622–31. http://dx.doi.org/10.1091/mbc.e17-06-0392.

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Cell shape changes such as cytokinesis are driven by the actomyosin contractile cytoskeleton. The molecular rearrangements that bring about contractility in nonmuscle cells are currently debated. Specifically, both filament sliding by myosin motors, as well as cytoskeletal cross-linking by myosins and nonmotor cross-linkers, are thought to promote contractility. Here we examined how the abundance of motor and nonmotor cross-linkers affects the speed of cytokinetic furrowing. We built a minimal model to simulate contractile dynamics in the Caenorhabditis elegans zygote cytokinetic ring. This model predicted that intermediate levels of nonmotor cross-linkers are ideal for contractility; in vivo, intermediate levels of the scaffold protein anillin allowed maximal contraction speed. Our model also demonstrated a nonlinear relationship between the abundance of motor ensembles and contraction speed. In vivo, thorough depletion of nonmuscle myosin II delayed furrow initiation, slowed F-actin alignment, and reduced maximum contraction speed, but partial depletion allowed faster-than-expected kinetics. Thus, cytokinetic ring closure is promoted by moderate levels of both motor and nonmotor cross-linkers but attenuated by an over-abundance of motor and nonmotor cross-linkers. Together, our findings extend the growing appreciation for the roles of cross-linkers in cytokinesis and reveal that they not only drive but also brake cytoskeletal remodeling.

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Robinson, Christopher L., Richard D. Evans, Kajana Sivarasa, Jose S. Ramalho, Deborah A. Briggs, and Alistair N. Hume. "The adaptor protein melanophilin regulates dynamic myosin-Va:cargo interaction and dendrite development in melanocytes." Molecular Biology of the Cell 30, no. 6 (March 15, 2019): 742–52. http://dx.doi.org/10.1091/mbc.e18-04-0237.

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The regulation of organelle transport by the cytoskeleton is fundamental for eukaryotic survival. Cytoskeleton motors are typically modular proteins with conserved motor and diverse cargo-binding domains. Motor:cargo interactions are often indirect and mediated by adaptor proteins, for example, Rab GTPases. Rab27a, via effector melanophilin (Mlph), recruits myosin-Va (MyoVa) to melanosomes and thereby disperses them into melanocyte dendrites. To better understand how adaptors regulate motor:cargo interaction, we used single melanosome fluorescence recovery after photobleaching (smFRAP) to characterize the association kinetics among MyoVa, its adaptors, and melanosomes. We found that MyoVa and Mlph rapidly recovered after smFRAP, whereas Rab27a did not, indicating that MyoVa and Mlph dynamically associate with melanosomes and Rab27a does not. This suggests that dynamic Rab27a:effector interaction rather than Rab27a melanosome:cytosol cycling regulates MyoVa:melanosome association. Accordingly, a Mlph-Rab27a fusion protein reduced MyoVa smFRAP, indicating that it stabilized melanosomal MyoVa. Finally, we tested the functional importance of dynamic MyoVa:melanosome interaction. We found that whereas a MyoVa-Rab27a fusion protein dispersed melanosomes in MyoVa-deficient cells, dendrites were significantly less elongated than in wild-type cells. Given that dendrites are the prime sites of melanosome transfer from melanocytes to keratinocytes, we suggest that dynamic MyoVa:melanosome interaction is important for pigmentation in vivo.

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Caremani, Marco, Francesca Pinzauti, Massimo Reconditi, Gabriella Piazzesi, Ger J. M. Stienen, Vincenzo Lombardi, and Marco Linari. "Size and speed of the working stroke of cardiac myosin in situ." Proceedings of the National Academy of Sciences 113, no. 13 (March 16, 2016): 3675–80. http://dx.doi.org/10.1073/pnas.1525057113.

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The power in the myocardium sarcomere is generated by two bipolar arrays of the motor protein cardiac myosin II extending from the thick filament and pulling the thin, actin-containing filaments from the opposite sides of the sarcomere. Despite the interest in the definition of myosin-based cardiomyopathies, no study has yet been able to determine the mechanokinetic properties of this motor protein in situ. Sarcomere-level mechanics recorded by a striation follower is used in electrically stimulated intact ventricular trabeculae from the rat heart to determine the isotonic velocity transient following a stepwise reduction in force from the isometric peak force TP to a value T (0.8–0.2 TP). The size and the speed of the early rapid shortening (the isotonic working stroke) increase by reducing T from ∼3 nm per half-sarcomere (hs) and 1,000 s−1 at high load to ∼8 nm⋅hs−1 and 6,000 s−1 at low load. Increases in sarcomere length (1.9–2.2 μm) and external [Ca2+]o (1–2.5 mM), which produce an increase of TP, do not affect the dependence on T, normalized for TP, of the size and speed of the working stroke. Thus, length- and Ca2+-dependent increase of TP and power in the heart can solely be explained by modulation of the number of myosin motors, an emergent property of their array arrangement. The motor working stroke is similar to that of skeletal muscle myosin, whereas its speed is about three times slower. A new powerful tool for investigations and therapies of myosin-based cardiomyopathies is now within our reach.

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Caramani, Marco, Luca Melli, Mario Dolfi, Vincenzo Lombardi, and Marco Linari. "Half-Sarcomere Mechanics and Energetics Indicate that Myosin Motors Slip Between Two Consecutive Actin Monomers during their Working Stroke." Biophysical Journal 102, no. 3 (January 2012): 17a. http://dx.doi.org/10.1016/j.bpj.2011.11.118.

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Hai, Chi-Ming, and Hak Rim Kim. "An expanded latch-bridge model of protein kinase C-mediated smooth muscle contraction." Journal of Applied Physiology 98, no. 4 (April 2005): 1356–65. http://dx.doi.org/10.1152/japplphysiol.00834.2004.

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A thin-filament-regulated latch-bridge model of smooth muscle contraction is proposed to integrate thin-filament-based inhibition of actomyosin ATPase activity with myosin phosphorylation in the regulation of smooth muscle mechanics. The model included two latch-bridge cycles, one of which was identical to the four-state model as proposed by Hai and Murphy ( Am J Physiol Cell Physiol 255: C86–C94, 1988), whereas the ultraslow cross-bridge cycle has lower cross-bridge cycling rates. The model-fitted phorbol ester induced slow contractions at constant myosin phosphorylation and predicted steeper dependence of force on myosin phosphorylation in phorbol ester-stimulated smooth muscle. By shifting cross bridges between the two latch-bridge cycles, the model predicts that a smooth muscle cell can either maintain force at extremely low-energy cost or change its contractile state rapidly, if necessary. Depending on the fraction of cross bridges engaged in the ultraslow latch-bridge cycle, the model predicted biphasic kinetics of smooth muscle mechanics and variable steady-state dependencies of force and shortening velocity on myosin phosphorylation. These results suggest that thin-filament-based regulatory proteins may function as tuners of actomyosin ATPase activity, thus allowing a smooth muscle cell to have two discrete cross-bridge cycles with different cross-bridge cycling rates.

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Miller, Mark S., Nicholas G. Bedrin, Philip A. Ades, Bradley M. Palmer, and Michael J. Toth. "Molecular determinants of force production in human skeletal muscle fibers: effects of myosin isoform expression and cross-sectional area." American Journal of Physiology-Cell Physiology 308, no. 6 (March 15, 2015): C473—C484. http://dx.doi.org/10.1152/ajpcell.00158.2014.

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Skeletal muscle contractile performance is governed by the properties of its constituent fibers, which are, in turn, determined by the molecular interactions of the myofilament proteins. To define the molecular determinants of contractile function in humans, we measured myofilament mechanics during maximal Ca2+-activated and passive isometric conditions in single muscle fibers with homogenous (I and IIA) and mixed (I/IIA and IIA/X) myosin heavy chain (MHC) isoforms from healthy, young adult male ( n = 5) and female ( n = 7) volunteers. Fibers containing only MHC II isoforms (IIA and IIA/X) produced higher maximal Ca2+-activated forces over the range of cross-sectional areas (CSAs) examined than MHC I fibers, resulting in higher (24–42%) specific forces. The number and/or stiffness of the strongly bound myosin-actin cross bridges increased in the higher force-producing MHC II isoforms and, in all isoforms, better predicted force than CSA. In men and women, cross-bridge kinetics, in terms of myosin attachment time and rate of myosin force production, were independent of CSA, although women had faster (7–15%) kinetics. The relative proportion of cross bridges and/or their stiffness was reduced as fiber size increased, causing a decline in specific force. Results from our examination of molecular mechanisms across the range of physiological CSAs explain the variation in specific force among the different fiber types in human skeletal muscle, which may have relevance to understanding how various physiological and pathophysiological conditions modulate single-fiber and whole muscle contractility.

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47

Gao, Bin, Jing Hua Zhu, and Wen Chang Lang. "Structural Analysis for an Ultra-Precision Machine Slide by FEM Based on Applied Mechanics." Advanced Materials Research 496 (March 2012): 321–24. http://dx.doi.org/10.4028/www.scientific.net/amr.496.321.

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Micro/nano machining becomes more and more important and popular. Ultra-precision machines are the fundamentals. Aiming at design and developing an ultra-precision machine tool for micro/nano machining, the slide, one of the most important part of the machine has been analyzed by FEM. The software Abaqus has been used for the analysis. Based on the full load created by the coils and permanent magnet of the linear motors, the kinetics characteristics have been analyzed. According to the analytical results, the slide structure has been optimized to fulfill the requirements of the developed micro/nano machine tool.

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Pertici, Irene, Manuel H. Taft, Johannes N. Greve, Roman Fedorov, Marco Caremani, and Dietmar J. Manstein. "Allosteric modulation of cardiac myosin mechanics and kinetics by the conjugated omega‐7,9 trans‐fat rumenic acid." Journal of Physiology 599, no. 15 (June 2021): 3639–61. http://dx.doi.org/10.1113/jp281563.

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49

Fouchard, Jonathan, Tom P. J. Wyatt, Amsha Proag, Ana Lisica, Nargess Khalilgharibi, Pierre Recho, Magali Suzanne, Alexandre Kabla, and Guillaume Charras. "Curling of epithelial monolayers reveals coupling between active bending and tissue tension." Proceedings of the National Academy of Sciences 117, no. 17 (April 13, 2020): 9377–83. http://dx.doi.org/10.1073/pnas.1917838117.

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Epithelial monolayers are two-dimensional cell sheets which compartmentalize the body and organs of multicellular organisms. Their morphogenesis during development or pathology results from patterned endogenous and exogenous forces and their interplay with tissue mechanical properties. In particular, bending of epithelia is thought to result from active torques generated by the polarization of myosin motors along their apicobasal axis. However, the contribution of these out-of-plane forces to morphogenesis remains challenging to evaluate because of the lack of direct mechanical measurement. Here we use epithelial curling to characterize the out-of-plane mechanics of epithelial monolayers. We find that curls of high curvature form spontaneously at the free edge of epithelial monolayers devoid of substrate in vivo and in vitro. Curling originates from an enrichment of myosin in the basal domain that generates an active spontaneous curvature. By measuring the force necessary to flatten curls, we can then estimate the active torques and the bending modulus of the tissue. Finally, we show that the extent of curling is controlled by the interplay between in-plane and out-of-plane stresses in the monolayer. Such mechanical coupling emphasizes a possible role for in-plane stresses in shaping epithelia during morphogenesis.

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Gregorich, Zachery R., Jitandrakumar R. Patel, Wenxuan Cai, Ziqing Lin, Rachel Heurer, Daniel P. Fitzsimons, Richard L. Moss, and Ying Ge. "Deletion of Enigma Homologue from the Z-disc slows tension development kinetics in mouse myocardium." Journal of General Physiology 151, no. 5 (January 14, 2019): 670–79. http://dx.doi.org/10.1085/jgp.201812214.

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Enigma Homologue (ENH) is a component of the Z-disc, a structure that anchors actin filaments in the contractile unit of muscle, the sarcomere. Cardiac-specific ablation of ENH protein expression causes contractile dysfunction that ultimately culminates in dilated cardiomyopathy. However, whether ENH is involved in the regulation of myocardial contractility is unknown. To determine if ENH is required for the mechanical activity of cardiac muscle, we analyze muscle mechanics of isolated trabeculae from the hearts of ENH+/+ and ENH−/− mice. We detected no differences in steady-state mechanical properties but show that when muscle fibers are allowed to relax and then are restretched, the rate at which tension redevelops is depressed in ENH−/− mouse myocardium relative to that in ENH+/+ myocardium. SDS-PAGE analysis demonstrated that the expression of β-myosin heavy chain is increased in ENH−/− mouse myocardium, which could partially, but not completely, account for the depression in tension redevelopment kinetics. Using top-down proteomics analysis, we found that the expression of other thin/thick filament regulatory proteins is unaltered, although the phosphorylation of a cardiac troponin T isoform, cardiac troponin I, and myosin regulatory light chain is decreased in ENH−/− mouse myocardium. Nevertheless, these alterations are very small and thus insufficient to explain slowed tension redevelopment kinetics in ENH−/− mouse myocardium. These data suggest that the ENH protein influences tension redevelopment kinetics in mouse myocardium, possibly by affecting cross-bridge cycling kinetics. Previous studies also indicate that ablation of specific Z-disc proteins in myocardium slows contraction kinetics, which could also be a contributing factor in this study.

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Journal articles on the topic 'Mechanics and kinetics of myosin motors'

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