Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2010 Aug 18;5(8):e12043. doi: 10.1371/journal.pone.0012043.
We consider a focal adhesion to be made up of molecular complexes, each consisting of a ligand, an integrin molecule, and associated plaque proteins. Free energy changes drive the binding and unbinding of these complexes and thereby controls the focal adhesion's dynamic modes of growth, treadmilling and resorption.
We have identified a competition among four thermodynamic driving forces for focal adhesion dynamics: (i) the work done during the addition of a single molecular complex of a certain size, (ii) the chemical free energy change associated with the addition of a molecular complex, (iii) the elastic free energy change associated with deformation of focal adhesions and the cell membrane, and (iv) the work done on a molecular conformational change. We have developed a theoretical treatment of focal adhesion dynamics as a nonlinear rate process governed by a classical kinetic model. We also express the rates as being driven by out-of-equilibrium thermodynamic driving forces, and modulated by kinetics. The mechanisms governed by the above four effects allow focal adhesions to exhibit a rich variety of behavior without the need to introduce special constitutive assumptions for their response. For the reaction-limited case growth, treadmilling and resorption are all predicted by a very simple chemo-mechanical model. Treadmilling requires symmetry breaking between the ends of the focal adhesion, and is achieved by driving force (i) above. In contrast, depending on its numerical value (ii) causes symmetric growth, resorption or is neutral, (iii) causes symmetric resorption, and (iv) causes symmetric growth. These findings hold for a range of conditions: temporally-constant force or stress, and for spatially-uniform and non-uniform stress distribution over the FA. The symmetric growth mode dominates for temporally-constant stress, with a reduced treadmilling regime.
In addition to explaining focal adhesion dynamics, this treatment can be coupled with models of cytoskeleton dynamics and contribute to the understanding of cell motility.
我们认为粘着斑由分子复合物组成，每个复合物由配体、整合素分子和相关斑蛋白组成。自由能变化驱动这些复合物的结合和解离，从而控制粘着斑的动态生长、 treadmilling 和吸收模式。
我们已经确定了四种热力学驱动力在粘着斑动力学中的竞争：（i）添加一定大小的单个分子复合物所做的功，（ii）添加分子复合物相关的化学自由能变化，（iii）粘着斑和细胞膜变形相关的弹性能自由能变化，（iv）分子构象变化所做的功。我们已经开发了一种粘着斑动力学的理论处理方法，作为由经典动力学模型控制的非线性速率过程。我们还将速率表示为由非平衡热力学驱动力驱动，并由动力学调节。上述四种效应的机制允许粘着斑表现出丰富的行为，而无需对其响应引入特殊的本构假设。对于反应限制的生长、 treadmilling 和吸收，都可以通过一个非常简单的化学机械模型来预测。 treadmilling 需要粘着斑两端的对称性破坏，由驱动力（i）驱动。相比之下，取决于其数值（ii）导致对称生长、吸收或中性，（iii）导致对称吸收，（iv）导致对称生长。这些发现适用于一系列条件：时间恒定的力或应力，以及 FA 上空间均匀和非均匀的应力分布。对于时间恒定的应力，对称生长模式占主导地位， treadmilling 范围减小。
除了解释粘着斑动力学外，这种处理方法还可以与细胞骨架动力学模型相结合，有助于理解细胞运动。
