Department of Biomechanics, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
Phys Rev E. 2016 Apr;93:042403. doi: 10.1103/PhysRevE.93.042403. Epub 2016 Apr 7.
The kinetic preference of actin-binding proteins to actin filaments is altered by external forces on the filament. Such an altered kinetic preference is largely responsible for remodeling the actin cytoskeletal structure in response to intracellular forces. During remodeling, actin-binding proteins and actin filaments interact under isothermal conditions, because the cells are homeostatic. In such a temperature homeostatic state, we can rigorously and thermodynamically link the chemical potential of actin-binding proteins to stresses on the actin filaments. From this relationship, we can construct a physical model that explains the force-dependent kinetic preference of actin-binding proteins to actin filaments. To confirm the model, we have analyzed the mechanosensitive alternation of the kinetic preference of Arp2/3 and cofilin to actin filaments. We show that this model captures the qualitative responses of these actin-binding proteins to the forces, as observed experimentally. Moreover, our theoretical results demonstrate that, depending on the structural parameters of the binding region, actin-binding proteins can show different kinetic responses even to the same mechanical signal tension, in which the double-helix nature of the actin filament also plays a critical role in a stretch-twist coupling of the filament.
肌动蛋白结合蛋白对肌动蛋白丝的动力学偏好会受到纤维上外力的改变。这种改变的动力学偏好在很大程度上负责响应细胞内力重塑肌动蛋白细胞骨架结构。在重塑过程中，肌动蛋白结合蛋白和肌动蛋白丝在等温条件下相互作用，因为细胞是处于动态平衡的。在这种温度恒态下，我们可以严格地从热力学上将肌动蛋白结合蛋白的化学势与肌动蛋白丝上的应力联系起来。从这个关系中，我们可以构建一个物理模型来解释肌动蛋白结合蛋白对肌动蛋白丝的力依赖性动力学偏好。为了验证该模型，我们分析了肌动蛋白结合蛋白（如 Arp2/3 和丝切蛋白）对肌动蛋白丝的力学敏感性动力学偏好的改变。我们表明，该模型捕捉到了这些肌动蛋白结合蛋白对力的定性响应，这与实验观察结果一致。此外，我们的理论结果表明，取决于结合区域的结构参数，即使是相同的机械信号张力，肌动蛋白结合蛋白也可以表现出不同的动力学响应，其中肌动蛋白丝的双螺旋性质在丝的拉伸-扭转耦联中也起着关键作用。
