Bipolar myosin II filaments engage actin filament arrays to generate contractile forces in both muscle and non-muscle cells. Key determinants of actomyosin force generation include the mechanochemistry of individual motors, motor filament size, and the compliance and turnover of actin filament arrays. How these properties interact to control rate, magnitude, and mechanosensitivity of force production remains poorly understood. Here, we extend a simple myosin II cross-bridge model to consider an ensemble of myosin motors engaging a single actin filament with an elastic tether. Consistent with previous work, we find that the duration of actin engagement and average force are highly sensitive to changes in ensemble size(Nheads) , motor duty ratio (dr), and environmental stiffness(k). Catch-bond kineticsshared by myosin II isoforms sharpen this sensitivity through positive feedback such that increases in Nheads, dr, or k above threshold values drive a rapid transition from non-processive to processive engagement. Tuning motor parameters to match different myosinII isoforms suggest that myosin filaments are poised to respond sharply to environmental stiffness or externally applied force. Thus, force production by myosin filaments is subject to switch-like control via tunable internal properties or mechanical context. We show further that for processive motors, the time required to build to stall (tbuild) scales with Fmax/(k*Vmax), where Fmax is the ensemble stall force and Vmax is the unloaded gliding velocity of the motor ensemble. Thus, increased environmental stiffnesspromotes faster force-buildup even without the myosin catch-bond, and force production will be limited when tbuild exceeds time scales of force relaxation such as actin turnover. Together, these results reveal how motor filament properties and environmental mechanics shape force production by actomyosin networks .
Myosin II isoforms with varying mechanochemistry and filament size interact with filamentous actin (F-actin) networks to generate contractile forces in cells. How their properties control force production in environments with varying stiffness is poorly understood. Here, we incorporated literature values for properties of myosin II isoforms into a cross-bridge model . Similar actin gliding speeds and force-velocity curves expected from previous experiments were observed. Motor force output on an elastic load was regulated by two timescales--that of their attachment to F-actin, which varied sharply with the ensemble size , motor duty ratio , and external load, and that of force build up, which scaled with ensemble stall force, gliding speed, and load stiffness. While such regulation did not require force-dependent kinetics, the myosin catch bond produced positive feedback between attachment time and force to trigger switch-like transitions from short attachments and small forces to high force-generating runs at threshold parameter values. Parameters representing skeletal muscle myosin, non-muscle myosin IIB, and non-muscle myosin IIA revealed 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 build-up times that exceed physiological timescales, and (3) small assemblies of low-duty ratio motors operating at intermediate speeds may respond sharply to changes in mechanical context--at low forces or stiffness, they serve as low affinity cross-links but they can transition to effective force production via the positive feedback mechanism described above. These results reveal how myosin isoform properties may be tuned to produce force and respond to mechanical cues in their environment .
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Bipolar myosin II filaments engage actin filament arrays
Myosin II isoforms with varying mechanochemistry and filament size interact with filamentous actin (F-actin) networks
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both muscle and non-muscle cells. Key determinants of actomyosin force generation include the mechanochemistry of individual motors, motor filament size, and the compliance and turnover of actin filament arrays. How these properties interact to control rate, magnitude, and mechanosensitivity of force production remains
cells. How their properties control force production in environments with varying stiffness is
R
extend a simple myosin II
incorporated literature values for properties of myosin II isoforms into a
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to consider an ensemble of myosin motors engaging a single actin filament with an elastic tether. Consistent with previous work, we find that the duration of actin engagement and average force are highly sensitive to changes in ensemble size(Nheads)
. Similar actin gliding speeds and force-velocity curves expected from previous experiments were observed. Motor force output on an elastic load was regulated by two timescales--that of their attachment to F-actin, which varied sharply with the ensemble size
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(dr), and environmental stiffness(k). Catch-bond kineticsshared by myosin II isoforms sharpen this sensitivity through positive feedback such that increases in Nheads, dr, or k above threshold values drive a rapid transition from non-processive to processive engagement. Tuning motor parameters to match different myosinII isoforms suggest that myosin filaments are poised to respond sharply to environmental stiffness or externally applied force. Thus, force production by myosin filaments is subject to
, and external load, and that of force build up, which scaled with ensemble stall force, gliding speed, and load stiffness. While such regulation did not require force-dependent kinetics, the myosin catch bond produced positive feedback between attachment time and force to trigger
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control via tunable internal properties or mechanical context. We show further that for processive motors, the time required to build to stall (tbuild) scales with Fmax/(k*Vmax), where Fmax is the ensemble stall force
transitions from short attachments and small forces to high force-generating runs at threshold parameter values. Parameters representing skeletal muscle myosin, non-muscle myosin IIB,
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Vmax is the unloaded gliding velocity of the motor ensemble. Thus, increased environmental stiffnesspromotes faster force-buildup even without the myosin catch-bond, and force production will be limited when tbuild exceeds time scales of force relaxation such as actin turnover. Together, these
non-muscle myosin IIA revealed 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 build-up times that exceed physiological timescales, and (3) small assemblies of low-duty ratio motors operating at intermediate speeds may respond sharply to changes in mechanical context--at low forces or stiffness, they serve as low affinity cross-links but they can transition to effective force production via the positive feedback mechanism described above. These
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motor filament properties and environmental mechanics shape force production by actomyosin networks
myosin isoform properties may be tuned to produce force and respond to mechanical cues in their environment