Viscoelastic Cytoskeletal-Membrane Mechanics: Hybrid Discrete-Continuum Stochastic Approaches

粘弹性细胞骨架膜力学：混合离散连续随机方法

• 批准号: 2306345
• 负责人: Paul Atzberger
• 金额: $ 39.98万
• 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: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2306345&HistoricalAwards=false
• 关键词: Viscoelastic; Cytoskeletal; Membrane; Mechanics; Hybrid

Cells are the fundamental units of life. In cell biology, many biological functions require the generation and coordination of complex mechanical events distributed throughout individual or populations of cells. This includes the generation and control of cellular motions in response to environmental signals of toxins or nutrients, generation of forces during cell division, and regulation of growth within tissues. Understanding of the roles of conditions arising in diseases, development of therapeutics and vaccines, engineering of bioreactors, and development of novel materials calls for advanced quantitative methods for studying cell mechanics. A central challenge in cell mechanics is to understand the principles by which larger scale mechanics arise from the smaller scale molecular-level events. This project develops new mathematical modeling paradigms and simulation software tools for investigating cell mechanics over multiple scales. This includes contributions from cell membranes and the cytoskeleton, which are structures providing the mechanical support maintaining the cell shape and internal organization. The methods capture contributions including the roles of the geometry, elastic structures, fluid mechanics, and fluctuations. Outreach activities are planned for engaging diverse and under-represented students at the University of California Santa Barbara and in the local community. This includes working with local area K-12 schools and colleges on programs to engage students on topics in the sciences, mathematics, and computation. Educational activities are also planned providing unique opportunities to train the next generation of researchers and students on recent emerging quantitative methods at the interface of mathematics and biology. The project addresses challenges in cell mechanics by providing new theoretical and computational stochastic approaches for handling molecular-level interactions and kinetics spanning over a hierarchy of scales. This includes regulation of the viscoelastic mechanics of protein-laiden lipid bilayer membranes, cytoskeletal filament rearrangements driven by cross-linked motor proteins, and cytoskeleton-membrane interactions. The project develops new stochastic computational methods for capturing both continuum and discrete contributions from the elastic mechanics, hydrodynamic coupling, geometry, and fluctuations. Stochastic numerical methods and efficient solvers and samplers are developed for handling the geometry of curved surfaces and general bulk domains. The methods draw on results from differential geometry and formulate unstructured discretizations building on finite element methods and meshless approaches. The methods will be used to study mechanisms underlying the mechanics of cytoskeleton-membrane interactions and in vitro active soft materials consisting of reconstituted cytoskeletal elements. This includes processes playing important roles in blebbing during initiation of cell motility and the generation of cytoskeletal forces. For the introduced modeling approaches and computational methods, software tools also will be developed and released with C++/python interfaces allowing for performing general simulations and analysis of phenomena in cell mechanics, complex fluids, and soft materials.This project is jointly funded by the Mathematical Biology and Computational Mathematics Programs at the Division of Mathematical Sciences and the Physics of Living Systems Program at the Division of Physics.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.

细胞是生命的基本单位。在细胞生物学中，许多生物功能需要产生和协调分布在单个细胞或细胞群中的复杂机械事件。这包括响应毒素或营养物的环境信号而产生和控制细胞运动，在细胞分裂期间产生力，以及调节组织内的生长。理解疾病中出现的条件的作用，治疗和疫苗的开发，生物反应器的工程，以及新材料的开发，需要先进的定量方法来研究细胞力学。细胞力学的一个核心挑战是理解从较小尺度的分子水平事件中产生较大尺度力学的原理。该项目开发新的数学建模范式和模拟软件工具，用于研究多尺度的细胞力学。这包括来自细胞膜和细胞骨架的贡献，细胞膜和细胞骨架是提供维持细胞形状和内部组织的机械支撑的结构。该方法捕获的贡献，包括几何形状，弹性结构，流体力学和波动的作用。计划开展外联活动，让加州圣巴巴拉大学和当地社区的多样化和代表性不足的学生参与进来。这包括与当地K-12学校和学院合作，让学生参与科学，数学和计算方面的课程。教育活动也计划提供独特的机会，培训下一代的研究人员和学生在数学和生物学的接口最近出现的定量方法。 该项目通过提供新的理论和计算随机方法来处理跨越尺度层次的分子水平相互作用和动力学，从而解决细胞力学中的挑战。这包括蛋白质-脂双层膜的粘弹性力学的调节，由交联的马达蛋白驱动的细胞骨架丝重排，以及细胞膜-膜相互作用。该项目开发了新的随机计算方法，用于捕获来自弹性力学、流体动力学耦合、几何和波动的连续和离散贡献。随机数值方法和有效的求解器和采样器的开发处理曲面和一般散装域的几何形状。这些方法利用微分几何的结果，并在有限元方法和无网格方法的基础上制定非结构化离散化。这些方法将用于研究细胞骨架-膜相互作用的机制和由重组细胞骨架元素组成的体外活性软材料。这包括在启动细胞运动和产生细胞骨架力期间在起泡中发挥重要作用的过程。对于引入的建模方法和计算方法，还将开发软件工具，并使用C++/python接口发布，允许对细胞力学，复杂流体，该项目由数学科学部的数学生物学和计算数学项目以及生命系统物理项目共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。