肌球蛋白II纤维在柔顺网络中的力生成
Force generation by Myosin II Filaments in Compliant Networks
摘要：
肌球蛋白II亚型具有不同的机械化学和细丝大小与丝状肌动蛋白（F-肌动蛋白）网络相互作用，在细胞中产生收缩力。它们的特性如何在不同刚度的环境中控制力的产生还知之甚少。在这里，我们将文献值肌球蛋白II异构体的性质到一个跨桥模型。观察到类似的肌动蛋白滑动速度和力-速度曲线预期从以前的实验。电机力输出的弹性负载调节两个时间尺度-他们的附件F-肌动蛋白，这与合奏大小，电机占空比，和外部负载急剧变化，和力的建立，这与合奏失速力，滑翔速度，和负载刚度缩放。虽然这种调节不需要力依赖性动力学，但肌球蛋白捕获键在附着时间和力之间产生正反馈，以触发从短附着和小力到阈值参数值下的高力产生运行的开关式转变。代表骨骼肌肌球蛋白、非肌肉肌球蛋白IIB和非肌肉肌球蛋白IIA的参数分别揭示了不同的行为机制：（1）快速、低占空比马达的大型组件在大范围的环境刚度上快速建立稳定的力，（2）慢速、高占空比马达的集合用作高亲和力交联，其力建立时间超过生理时间尺度，以及（3）在中速下运行的低占空比电动机的小组件可以对机械环境的变化作出急剧响应--在低力或刚度下，它们用作低亲和力交联，但是它们可以通过上述正反馈机制转变为有效的力产生。这些结果揭示了肌球蛋白同种型的特性如何被调节以产生力并对环境中的机械提示做出反应。
英文摘要：
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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