Computational Modeling of Cytoskeletal Contractility and Remodeling

CBET-0829205Mofrad细胞骨架的活性、收缩和重塑特性是许多细胞活动的中心。然而，目前还没有对这些现象进行量化的模型。这项研究的目的是将离散的纳米尺度的分子事件，如肌动蛋白-肌球蛋白相互作用，转化为细胞收缩和重塑操作的宏观尺度。细胞收缩能力的定量模型将被开发出来，反映细胞骨架的异质性、互联性和重塑性质。这样的模型对于解释细胞的微观和宏观尺度的力学行为是至关重要的，因为细胞骨架的远程相互连接和重组特征使其变得复杂。该模型对于解释由于细胞骨架的远程连接和重组特性而变得复杂的微观尺度和宏观尺度的细胞骨架功能是至关重要的。对微观和宏观尺度细胞骨架力学的实验观察将在细胞骨架的异质性、互连性和重塑特征的背景下进行解释。虽然机械转导和迁移等更复杂的细胞过程模型超出了本研究的直接范围，但这里开发的工具随后将帮助研究界以仅靠实验无法系统和定量探索的方式解决其他根本重要的问题。建议的模型将提供一个必要的工具，以促进我们对细胞机械传感和机械转导中的关键步骤的理解，因此具有强大的变革潜力，可以发现新的策略来缓解许多疾病，在这些疾病中，力学和生物化学的相互作用是关键的(例如动脉粥样硬化、钙化性主动脉狭窄、癌症等)。此外，PIS计划开发新的课程，并扩大来自代表性不足群体的学生的参与。

CBET-0829205MofradThe active, contractile, and remodeling nature of the cytoskeleton is central to many cellular activities. No model yet exists, however, for quantifying these phenomena. The objective of this research is to translate discrete nano-scale molecular events like actin-myosin interaction into a macro-scale at which the cellular contractility and remodeling operate. A quantitative model of cell contractility will be developed reflecting the heterogenous, interconnected and remodeling nature of the cytoskeleton. Such a model is crucial to interpreting the micro-scale and macro-scale mechanical behavior of the cell that is complicated by the long-range interconnections and reorganizations characteristics of the cytoskeleton. The proposed model is crucial to interpreting the micro-scale and macro-scale cytoskeletal functions that are complicated by the long-range interconnections and reorganizations characteristics of the cytoskeleton. The experimental observations on micro- and macro-scale cytoskeletal mechanics will be interpreted in the context of the heterogeneous, interconnected and remodeling character of the cytoskeleton. While a model of more complex cell processes such as mechanotransduction and migration are beyond the immediate scope of this research, the tools developed here will subsequently aide the research community in addressing other fundamentally important issues in a manner that cannot be explored systematically and quantitatively by experiments alone. The proposed model will offer a necessary tool for advancing our understanding of a key step in cellular mechanosensing and mechanotransduction, and has therefore a strong transformative potential for discovering new strategies to mitigate many diseases where the interplay of mechanics and biochemistry are critical (e.g. atherosclerosis, calcific aortic stenosis, cancer, ...)On an outreach level, the PI plans to disseminate the research through a website dedicated to cellular and molecular mechanisms. In addition, the PIs plan to develop new courses and to broaden the participation of students from underrepresented groups.