title: Isoforms Confer Characteristic Force Generation and Mechanosensation by Myosin II Filaments.
abstract: Myosin II isoforms with varying mechanochemistry and filament size interact with filamentous actin (F-actin) arrays to generate contractile forces in muscle and nonmuscle cells. How myosin II force production is shaped by isoform-specific motor properties and environmental stiffness remains poorly understood. Here, we used computer simulations to analyze force production by an ensemble of myosin motors against an elastically tethered actin filament. We found that force output depends on two timescales: the duration of F-actin attachment, which varies sharply with the ensemble size, motor duty ratio, and external load; and the time to build force, which scales with the ensemble stall force, gliding speed, and environmental stiffness. Although force-dependent kinetics were not required to sense changes in stiffness, the myosin catch bond produced positive feedback between the attachment time and force to trigger switch-like transitions from transient attachments, generating small forces, to high-force-generating runs. Using parameters representative of skeletal muscle myosin, nonmuscle myosin IIB, and nonmuscle myosin IIA revealed three distinct regimes of behavior, respectively: 1) large assemblies of fast, low-duty ratio motors rapidly build stable forces over a large range of environmental stiffness; 2) ensembles of slow, high-duty ratio motors serve as high-affinity cross-links with force buildup times that exceed physiological timescales; and 3) small assemblies of low-duty ratio motors operating at intermediate speeds are poised to respond sharply to changes in mechanical context-at low force or stiffness, they serve as low-affinity cross-links, but they can transition to force production via the positive-feedback mechanism described above. Together, these results reveal how myosin isoform properties may be tuned to produce force and respond to mechanical cues in their environment.
authors.affiliation: Biophysical Sciences Graduate Program, University of Washington, Friday Harbor, Washington; Institute for Biophysical Dynamics, University of Washington, Friday Harbor, Washington.
authors.forename: Samantha
authors.initials: S
authors.lastname: Stam
authors.affiliation: Center for Cell Dynamics, University of Washington, Friday Harbor, Washington.
authors.forename: Jon
authors.initials: J
authors.lastname: Alberts
authors.affiliation: Institute for Biophysical Dynamics, University of Washington, Friday Harbor, Washington; Physics Department, University of Chicago, Chicago, Illinois; James Franck Institute, University of Chicago, Chicago, Illinois; Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois. Electronic address: gardel@uchicago.edu.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Gardel
authors.affiliation: Institute for Biophysical Dynamics, University of Washington, Friday Harbor, Washington; Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, Illinois. Electronic address: emunro@uchicago.edu.
authors.forename: Edwin
authors.initials: E
authors.lastname: Munro
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D024462:Myosin Type II / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D024462:Myosin Type II