Active Mechanics and Remodeling of Cytoskeletal Networks

细胞骨架网络的主动力学和重塑

• 批准号: 1300514
• 负责人: Alexander Levine
• 金额: $ 39.7万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1300514&HistoricalAwards=false
• 关键词: Active; Mechanics; Remodeling; Cytoskeletal; Networks

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.

该奖项的研究目标是利用数值模拟和分析计算的结合来探索活性细胞骨架网络的非平衡力学。活细胞的细胞骨架是一个由丝状蛋白、交联分子和分子马达组成的化学复杂网络，驱动网络进入复杂且非平衡的稳态。该奖项下进行的研究将调查运动活动的状态如何调节该细丝网络的机械响应，以及交联剂的结合和解除结合如何有助于网络的结构重组和粘弹性。这些网络模型将针对简化的实验系统进行验证，然后应用于细胞如何与其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细丝网络的统计力学前沿问题提供新的见解，该问题涉及由于其内部的运动活动而导致其结构和弹性模量的演变。这一新见解将对理解活细胞的机制产生广泛的影响。具体来说，人们将更多地了解细胞如何向周围环境施加力并粘附到周围环境。这些特性对于阐明细胞运动和粘附具有主要的生理相关性。在这些研究过程中产生的数值模拟包也将使其他研究人员受益，这些研究人员寻求模拟工具来探索细胞骨架对力的响应或由于引入不同的交联分子而导致的活性网络进化的变化。该教育计划的重点是本科生和研究生阶段的工程和物理学课程开发，以便将生物力学更多地纳入获奖机构的主流。