Computational Modeling of Cytoskeletal Contractility and Remodeling

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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.