2007 NIH Director's Pioneer Award Program (DP1)

摘要 细胞和生物生物学中的一个主要挑战是了解活细胞生理学是如何 是由单个大分子的生物物理性质产生的。形态上的和 细胞黏附、迁移和分裂所需的细胞的物理行为取决于适当的 对被称为细胞骨架的多蛋白质机器的巨大层次进行空间和时间调节。 然而，当我们获得越来越多的关于个体属性的知识时， 细胞骨架蛋白，我们对其自组装和物理性质知之甚少。 形成物理结构的多蛋白质组合，将机械信息传递到细胞 长度刻度。例如，我们不理解单个分子如何产生力 马达被细胞骨架组件利用来调节形态发生和力的产生 在细胞水平上。目前对细胞细胞骨架物理行为的了解有 受到缺乏探索动态结构和物理结构的实验技术的限制 活细胞中介观细胞骨架组件的特性。我建议设立 研究活细胞中细胞骨架物质生物物理性质的实验工具 将凝聚态物理和分子细胞生物学的方法结合起来。这项工作将 确定新出现的细胞骨架组件的基本物理学，并将提供预测性 将我们对分子生物物理学的理解与细胞行为联系起来的分析模型。最后， 这项工作将影响由于身体调节不当而导致的疾病的治疗。 细胞的行为，包括癌症转移和心脏疾病。

ABSTRACT A major challenge in cell and organism biology is to understand how living cell physiology emerges from the biophysical properties of individual macromolecules. The morphological and physical behaviors of cells required for cell adhesion, migration and division depend on the proper spatial and temporal regulation of a vast hierarchy of multi-protein machines, called the cytoskeleton. However, while we are gaining increasing amounts of knowledge of properties of individual cytoskeletal proteins, we have very little knowledge about the self-assembly and physical properties of multi-protein assemblies that form physical structures to transmit mechanical information up to cellular length scales. For example, we do not understand how forces generated by individual molecular motors are exploited by cytoskeletal assemblies to regulate morphogenesis and force generation at the cellular level. Current understanding of the physical behavior of the cellular cytoskeleton has been limited both by the lack of experimental techniques to probe the dynamic structure and physical properties of mesoscopic cytoskeletal assemblies in living cells. I propose to establish the experimental tools to study the biophysical properties of cytoskeletal matter in living cells by integrating approaches from condensed matter physics with molecular cell biology. This work will identify the underlying physics of emergent cytoskeletal assemblies and will provide predictive analytical models to link our understanding of the biophysics of molecules to cell behaviors. Finally, this work will impact the treatment of diseases that are a result of misregulation of the physical behaviors of cells, including cancer metastasis and cardiac diseases.