Chemo-Mechanical Factors That Limit Cellular Force Generation
Chemo-Mechanical Factors That Limit Cellular Force Generation
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DOI：
10.3389/fphy.2022.831776
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发表时间：
2022-02
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影响因子：
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通讯作者：
Esteban Vazquez-Hidalgo;C. Farris;A. Rowat;Parag Katira
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作者：
Esteban Vazquez-Hidalgo;C. Farris;A. Rowat;Parag Katira
细胞的牵引力，是依赖于肌动蛋白-肌球蛋白活性是必要的许多发育和生理过程。随着牵引力作为一种有前途的癌症生物标志物的出现，越来越需要了解响应化学和机械线索的力产生。我们的目标是提出一个统一的建模框架，整合肌动蛋白-肌球蛋白活性，底物硬度，整合素键型，和粘附复合物的动力学来解释力如何在特定条件下发展。我们的模拟结果表明，基质刚度和肌球蛋白马达的数量有助于产生最大肌动蛋白-肌球蛋白力，但不能单独控制细胞传递到表面的力，即，牵引力。细胞和基质之间的键合动力学起着同样重要的作用。总的来说，我们发现，虽然细胞可以在单个应力纤维中产生大的肌动蛋白-肌球蛋白力（> 300 pN），但每个细胞-基质附着传递到表面的最大力仅达到这些值的一小部分（约300 pN）。50 pN）。牵引应力是单位面积内所有细胞-基质附着所传递的力的总和，是双相或S形的，随着基质刚度的增加，牵引应力取决于产生力的活性肌球蛋白马达的数量。最后，我们得出结论，< 1 μ m2的粘连产生广泛变化的牵引力，并且脉冲，力产生事件的大小和持续时间，是牵引应力的关键限制因素。
Cellular traction forces that are dependent on actin-myosin activity are necessary for numerous developmental and physiological processes. As traction force emerges as a promising cancer biomarker there is a growing need to understand force generation in response to chemical and mechanical cues. Our goal is to present a unified modeling framework that integrates actin-myosin activity, substrate stiffness, integrin bond type, and adhesion complex dynamics to explain how force develops under specific conditions. Our simulation results show that substrate stiffness and number of myosin motors contribute to the maximum actin-myosin forces that can be generated but do not solely control the force transmitted by the cells to the surface, i.e., the traction force. The kinetics of the bonds between the cell and the substrate plays an equally important role. Overall, we find that while the cell can generate large actin-myosin forces in individual stress fibers ( > 300 pN), the maximum force transmitted to the surface per cell-substrate attachment only reaches a fraction of these values (approx. 50 pN). Traction stress, the sum of forces transferred by all cell-substrate attachments in a unit area, is biphasic or sigmoidal with increasing substrate stiffness depending on the number of active myosin motors generating forces. Finally, we conclude that adhesions < 1 μm 2 generate widely variable traction forces and that impulse, the magnitude and duration of a force generating event, is a key limiting factor in traction stress.