CAREER: Fluid-structure interactions in cytoskeletal assemblies

电池是一种机械机器，由较小的机器组成，将化学能转化为力和运动。细胞力学是许多细胞过程的关键，包括细胞形状、细胞运动和细胞分裂。细胞机械的主要组成部分是细胞骨架，这是一个由微丝组成的高度动态的网络。细胞骨架细丝在附着在它们上并沿着它们行走的分子马达的力的作用下不断移动。这些运动在细胞内产生流动。这些诱导的流体-结构(细丝)相互作用是细胞骨架力学的关键，但在以前的研究中它们在很大程度上被忽略了。这项研究的目的是利用计算机模拟和数学建模来深入了解流体-结构相互作用和细胞流动对细胞骨架组织和力学的作用。研究和教育部分通过与大学的天文馆和科学中心(每年约16万名参观者)合作整合在一起，以创造身临其境的虚拟现实体验，以便参观者可以缩小到细胞大小并学习细胞力学。该小组将为高中教师制定课程并举办研讨会，以便在课堂上有意义地实施这些活动。细胞骨架是浸泡在细胞质液体中的细丝--包括肌动蛋白细丝和微管--和马达蛋白质的动态自组织组装。细胞骨架是细胞对外界机械刺激以及包括细胞运动和细胞分裂在内的许多细胞内机械过程做出反应的关键。细胞质流体和弹性纤维之间的非局部相互作用是决定细胞骨架的瞬时结构和力学的关键。然而，在细胞骨架组件的计算研究中，这些流体-结构相互作用在很大程度上被忽略了。首席研究人员最近开发了一个平台，用于模拟斯托克斯流动及其相关流动中聚合柔性长丝的大组件的动力学。这项提议的最终目标是利用这个计算平台来了解流体-结构相互作用和细胞质流动对细胞骨架组装的组织和力学的影响。本研究分为三个相互关联和相辅相成的目标。目标1和目标2的目的是对流体-结构相互作用的作用有一个基本的理解，对生理细节的依赖程度较低。这是通过在电子计算机中概括简化的微管组件的体外重组，并研究来自马达蛋白质的力(目标1)和(解聚)对微管组件的组织和流变学的影响来实现的。在目标3中，结合光电子显微镜和粒子跟踪数据与模拟来研究优雅线虫第一个细胞分裂中有丝分裂纺锤体的定位和组装。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The cell is a mechanical machine made of smaller machines that transform chemical energy to force and motion. Cell mechanics is key to many cellular processes, including cell shape, cell motility and cell division. The main component of cell's mechanical machinery is the cytoskeleton, which is a highly dynamic network of microscopic filaments. The cytoskeletal filaments are continuously moved by forces from molecular motors that attach to and walk along them. These movements generate flows inside the cell. These induced fluid-structures (filaments) interactions are key to the cytoskeleton mechanics; yet they have been largely ignored in previous studies. The purpose of this research is to use computer simulations and mathematical modelling to develop a deep understanding of the role of fluid-structure interactions and cellular flows on the cytoskeleton organization and mechanics. The research and educational component are integrated by partnering with the Planetarium and Science Center (approximately 160,000 annual visitors) at the university, to create an immersive Virtual Reality experience so that the visitors can shrink down to the cell size and learn about cell mechanics. The team will develop a curriculum and hold workshops for high school teachers for meaningful implementation of these activities in the classroom. The cytoskeleton is a dynamic self-organized assembly of filaments - including actin filaments and microtubules - and motor-proteins immersed in the cytoplasmic fluid. The cytoskeleton is key to the cell's response to external mechanical stimuli as well as many intracellular mechanical processes, including cell motility and cell division. The nonlocal interactions between the cytoplasmic fluid and the flexible filaments are key to determining the transient structure and mechanics of the cytoskeleton. Yet these fluid-structure interactions have been largely ignored in computational studies of cytoskeletal assemblies. The principal investigator has recently developed a platform for simulating the dynamics of large assemblies of polymerizing flexible filaments in Stokes flow and their associated flows. The ultimate goal of this proposal is to use this computational platform to understand the effect of fluid-structure interactions and cytoplasmic flows on the organization and mechanics of cytoskeletal assemblies. The research is divided into three connected and complimentary Aims. The purpose of Aim 1 and Aim 2 is to develop a fundamental understanding of the role of fluid-structure interactions that is less dependent on the physiological details. This is achieved by in silico recapitulation of simplified in vitro reconstitutions of microtubule assemblies, and studying the effect of forces from motor-proteins (Aim 1), and (de)polymerization (Aim 2) on the organization and rheology of microtubule assemblies. In Aim 3, light and electron microcopy and particle tracking data is combined with simulations to study the positioning and assembly of the mitotic spindle in the first cell division of Caenorhabditis elegans.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.