CAREER: Emergent Biological Mechanics of Cellular Microstructures

职业：细胞微观结构的新兴生物力学

• 批准号: 0956210
• 负责人: Paul Atzberger
• 金额: $ 43.52万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0956210&HistoricalAwards=false
• 关键词: CAREER; Emergent; Biological; Mechanics; Cellular

A fundamental problem in cell biology is to relate how molecular level events result in the emergent mechanics and functions of cellular structures. This is especially challenging since biological processes often exhibit organization and coupling over a wide hierarchy of spatial and temporal scales. This can be readily seen when observing cellular structures, such as the lipid-protein bilayer membrane encasing the cell or the intricate filament architecture of the cytoskeleton. It is expected that this organization is not only designed to have mechanics which allow the cell to resist outside perturbations from the environment, but also to be readily regulated and to provide feedback on cellular processes.The proposed research aims to contribute to this area by the formulation of new paradigms and the investigation of specific hypotheses. For lipid-protein membranes, mechanisms will be investigated for how mechanical stresses in the bilayer alter protein conformations, protein aggregation and depletion, and protein mobility. For the cytoskeleton, mechanisms will be investigated for how bulk mechanical properties change when augmenting the filament architecture and interactions through passive linkers and active motor proteins. These will be explored through a combination of large-scale computational simulation studies performed by the PI and through experimental studies carried out by collaborators. New mathematical and computational approaches will also be developed for the bridging of organizational scales in dynamic models of cell mechanics.The proposed research program is integrated with the mentoring and training of both undergraduate and graduate students for work at the interface of mathematics and the biological sciences.Proposed activities also include a number of educational and community outreach initiatives. This includes recruitment of students from under-represented groups leveraging the UC RISE and UC CAMP programs at UCSB, teaching an undergraduate freshman seminar course on mathematical biology, teaching a graduate special topics course on cell mechanics, and participation in the UCSB Math Circle for junior high school teachers and students. In the third year of funding, an interdisciplinary workshop focused on cell mechanics will be organized to facilitate the exchange of research results and to foster collaborations between mathematicians and experimental biologists.This project is co-funded by the Division of Mathematical Sciences and the Office of Cyber Infrastructure.

细胞生物学的一个基本问题是将分子水平事件如何导致细胞结构的新兴力学和功能。 这尤其具有挑战性，因为生物过程经常在空间和时间尺度的广泛层次结构上表现出组织和耦合。 观察细胞结构时，可以很容易地看到这一点，例如包围细胞的脂质蛋白双层膜或细胞骨架的错综复杂的细丝结构。 预计该组织不仅旨在具有允许细胞抵抗环境扰动的机制，而且还可以轻松调节并提供有关细胞过程的反馈。拟议的研究旨在通过制定新的范式来为该领域做出贡献，并对特定假设进行研究。 对于脂质 - 蛋白质膜，将研究机制，以改变双层中的机械应力改变蛋白质构象，蛋白质聚集和耗竭以及蛋白质迁移率。 对于细胞骨架，将研究机制，以通过被动接头和活性运动蛋白来增强细丝结构和相互作用时如何变化。 这些将通过PI进行的大规模计算模拟研究以及合作者进行的实验研究的结合来探讨这些。 还将开发新的数学和计算方法，以在细胞力学动态模型中的组织量表进行桥接。拟议的研究计划与本科生和研究生的指导和培训集成到数学和生物学科学界面上的工作。预先培训的活动还包括许多教育和社区脱颖而出的发起人。 这包括招募来自代表性不足的小组的学生，该小组利用UCSB的UC Rise和UC Camp计划，教授数学生物学的本科大一新生研讨会课程，教授细胞力学的研究生特殊主题，并参加初中高中老师和学生的UCSB Math Circle。 在资助的第三年中，将组织一个专注于细胞力学的跨学科研讨会，以促进研究结果的交流并促进数学家与实验生物学家之间的合作。该项目由数学科学和网络基础设施办公室共同资助。