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，许多生物学功能都需要生成和协调复杂的机械事件，分布在细胞的个体或人群中。这包括响应毒素或营养的环境信号的细胞运动的产生和控制，细胞分裂过程中的产生以及组织内生长的调节。了解在疾病中产生的疾病的作用，治疗和疫苗的发展，生物反应器的工程以及新型材料的开发，要求采用用于研究细胞力学的先进定量方法。细胞力学中的一个核心挑战是了解较大规模的分子级事件引起的较大规模力学的原理。该项目开发了新的数学建模范例和仿真软件工具，用于在多个尺度上研究细胞力学。这包括细胞膜和细胞骨架的贡献，这些结构是提供维持细胞形状和内部组织的机械支持的结构。这些方法捕获了贡献，包括几何，弹性结构，流体力学和波动的作用。计划在加利福尼亚大学圣塔芭芭拉分校和当地社区中吸引多样化和代表性的学生，以吸引外展活动。这包括与本地K-12学校和大学合作，开展课程，以使学生参与科学，数学和计算中的主题。还计划的教育活动提供了独特的机会，以培训下一代研究人员和学生在数学和生物学界面上的最新定量方法。 该项目通过提供新的理论和计算随机方法来处理分子级相互作用和跨越量表层次结构的动力学来解决细胞力学的挑战。这包括调节蛋白质内脂质双层膜的粘弹性力学，由交联的运动蛋白驱动的细胞骨架细丝重排以及细胞骨架膜相互作用。该项目开发了新的随机计算方法，用于捕获弹性力学，流体动力耦合，几何和波动的连续性和离散贡献。为处理弯曲表面和一般体积域的几何形状而开发了随机数值方法，有效的求解器和采样器。这些方法借鉴了差分几何形状的结果，并根据有限元方法和无网状方法制定了非结构化的离散化。该方法将用于研究细胞骨架 - 膜相互作用机制和由重构细胞骨架元件组成的体外活性软材料的机制。这包括在启动细胞运动和产生细胞骨架力的过程中发挥重要作用的过程。对于介绍的建模方法和计算方法，还将使用C ++/Python界面开发和发布软件工具，允许在细胞力学，复杂的流体和软材料中进行一般模拟和现象分析。该项目是由数学生物学和计算数学奖在数学系统范围内的数学分工和物理学分区的总体数学和计算数学计划共同资助的。 NSF的法定使命，并使用基金会的知识分子优点和更广泛的影响审查标准来评估值得支持。