Cytoplasmic streaming and amoeboid cell motility: Mathematical models and computational methods

细胞质流和变形细胞运动：数学模型和计算方法

• 批准号: 1226386
• 负责人: Robert Guy
• 金额: $ 11.94万
• 依托单位: University of California-Davis
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1226386&HistoricalAwards=false
• 关键词: Cytoplasmic; streaming; amoeboid; cell; motility

Recent experiments on cell locomotion through three-dimensional fibrous matrices have raised new questions about the basic mechanisms of cell locomotion. In particular, they have shown that some cells use pressure-driven protrusions called blebs to squeeze their way through the gaps in the matrix, and it has been hypothesized that this method of locomotion can be achieved without adhesive interactions with the surrounding environment. The goal of this project is to develop a comprehensive mathematical model of a blebbing cell and use this modeling framework to explore how cells use cytoplasmic streaming for locomotion. This model will be the first to provide an integrative picture of how local mechanical and chemical factors work together to drive directed cell locomotion. These models will involve the mechanochemical chemical interactions between the cytoskeleton, cytosol, cell membrane, extracellular fluid, and the surrounding solid structures. A necessary component to this project is accounting for the changing geometry of the cells. Given the complexity of the problem, efficient numerical simulations are needed to explore the models. The investigators develop a new mixed Eulerian-Lagrangian framework to unify the mathematical description of these complex interacting materials. Using this framework, new and efficient methods for solving the coupled equations that arise in the model are developed.Many problems in biology involve interactions between mechanics complex multiphase fluids, chemical reactions, and deforming structures. For example, the dynamics of growing bacterial biofilms and the transport of mucus in the respiratory system are two such processes. Our models and numerical methods can be adapted to explore these important complex systems. A graduate student will be trained as part of this research project. This project is ideally suited for training graduate students with the broad background necessary for research in mathematical biology and scientific computation. The student will interface directly with the experimental collaborators involved in the project to learn the essential skill of communicating ideas across disciplines.

最近关于细胞在三维纤维基质中运动的实验对细胞运动的基本机制提出了新的问题。特别是，他们已经表明，一些细胞使用称为气泡的压力驱动突起来挤压基质中的间隙，并且已经假设这种运动方法可以在没有与周围环境的粘附相互作用的情况下实现。 这个项目的目标是开发一个全面的数学模型的起泡细胞，并使用这个建模框架来探索细胞如何使用细胞质流动的运动。该模型将首次提供局部机械和化学因素如何共同作用以驱动定向细胞运动的综合图片。这些模型将涉及细胞骨架、细胞溶质、细胞膜、细胞外液和周围固体结构之间的机械化学化学相互作用。该项目的一个必要组成部分是考虑细胞的几何形状变化。鉴于问题的复杂性，需要有效的数值模拟来探索模型。 研究人员开发了一种新的混合欧拉-拉格朗日框架，以统一这些复杂相互作用材料的数学描述。在此框架下，发展了求解模型中耦合方程的新的有效方法。生物学中的许多问题涉及到力学、复杂的多相流体、化学反应和变形结构之间的相互作用。例如，生长细菌生物膜的动力学和呼吸系统中粘液的运输就是两个这样的过程。我们的模型和数值方法可以适用于探索这些重要的复杂系统。作为本研究项目的一部分，将培训一名研究生。该项目非常适合培养具有数学生物学和科学计算研究所需的广泛背景的研究生。学生将直接与参与项目的实验合作者进行交流，学习跨学科交流思想的基本技能。