CAREER: Emergent Biological Mechanics of Cellular Microstructures

细胞生物学中的一个基本问题是关于分子水平的事件如何导致细胞结构的紧急机械和功能。这尤其具有挑战性，因为生物过程往往表现出在空间和时间尺度的广泛等级上的组织和耦合。这在观察细胞结构时很容易看到，例如包裹细胞的脂质-蛋白质双层膜或细胞骨架复杂的细丝结构。期望这一组织不仅具有使细胞抵抗外界干扰的机制，而且易于调节并提供细胞过程的反馈。拟议的研究旨在通过制定新的范式和研究特定的假设来促进这一领域的发展。对于脂蛋白膜，将研究双层中的机械应力如何改变蛋白质构象、蛋白质聚集和耗尽以及蛋白质迁移率的机制。对于细胞骨架，将研究当通过被动连接物和主动马达蛋白增强细丝结构和相互作用时，整体机械性能如何变化的机制。这些将通过由国际和平研究所进行的大规模计算模拟研究和由合作者进行的实验研究相结合来探索。还将开发新的数学和计算方法，以便在细胞力学的动态模型中建立组织规模的桥梁。拟议的研究计划与本科生和研究生在数学和生物科学相结合的工作中的指导和培训相结合。拟议的活动还包括一些教育和社区外展倡议。这包括利用UCSB的UC Rise和UC Camp计划从代表性不足的群体中招募学生，教授关于数学生物学的本科新生研讨会课程，教授关于细胞力学的研究生专题课程，以及参加UCSB为初中教师和学生举办的数学圈。在资助的第三年，将举办一个以细胞力学为重点的跨学科工作坊，以促进研究成果的交流，并促进数学家和实验生物学家之间的合作。该项目由数学科学司和网络基础设施办公室共同资助。

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.