Active Mechanics and Remodeling of Cytoskeletal Networks

该奖项的研究目标是使用数值模拟和解析计算相结合的方法来探索主动细胞骨架网络的非平衡力学。活细胞的细胞骨架是由丝状蛋白质、交联分子和分子马达组成的复杂的化学网络，这些分子马达将网络驱动到复杂和非平衡的稳定状态。根据该奖项进行的研究将调查运动活动状态如何调整该细丝网络的机械响应，以及交联剂的结合和解绑如何有助于该网络的结构重组和粘弹性。这些网络模型将在简化的实验系统上得到验证，然后应用于细胞如何与环境进行机械相互作用的研究。如果成功，这些研究将为电机驱动的细丝网络统计力学中的一个前沿问题带来新的见解，该问题涉及到由于内部运动而导致的细丝网络结构和弹性模数的演变。这一新的见解将对理解活细胞的机制具有广泛的意义。具体地说，人们将了解更多关于细胞如何对其周围环境施加力并与其附着的知识。这些特性对于阐明细胞的运动和黏附具有重要的生理学意义。在这些研究过程中产生的数值模拟程序包也将使其他寻求模拟工具的研究人员受益，以探索细胞骨架对力或由于引入不同的交联剂分子而导致的活性网络进化中的变化的响应。教育计划的重点是在本科生和研究生水平上开发工程和物理课程，以便将生物力学更多地纳入获奖者机构的主流。

The research objective of this award is to use a combination of numerical simulation and analytic calculations to explore the nonequilibrium mechanics of active cytoskeletal networks. The cytoskeleton of living cells is a chemically complex network of filamentous proteins, cross-linking molecules, and molecular motors, which drive the network into a complex and nonequilibrium steady state. Studies conducted under this award will investigate how the state of motor activity can tune the mechanical response of this filament network, and how the binding and unbinding of cross linkers contributes to the structural reorganization and viscoelasticity of the network. These network models will be validated against simplified experimental systems and then applied to the study of how cells interact mechanically with their environment.If successful, these studies would generate new insight into a frontier problem in the statistical mechanics of motor-driven filament networks concerning the evolution of their structure and elastic moduli due to motor activity within them. This new insight would have broad implications for understanding the mechanics of living cells. Specifically, one would learn more about how cells exert forces on and adhere to their surroundings. These properties are of prime physiological relevance for elucidating cell motility and adhesion. The numerical simulation packages produced over the course of these studies will also benefit other researchers seeking simulation tools to explore the response of the cytoskeleton to forces or changes in the evolution of the active network due to the introduction of different cross linking molecules. The educational plan focuses on course development in engineering and physics at the undergraduate and graduate level in order to bring biomechanics more into the mainstream at the awardees' institution.