Systems Biophysics of Multiscale State Transitions in Cells and Tissues

细胞和组织多尺度状态转变的系统生物物理学

• 批准号: 10631113
• 负责人: Michael MAK
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-06 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631113
• 关键词: Architecture; Biology; Biophysics; Cells; Complex; Computing Methodologies; Cytoskeletal Modeling; Cytoskeleton; Extracellular Matrix; Goals; Mechanics; Molecular; Osmotic Pressure; Phenotype; System; Tissues; cell motility; crosslink; programs

Project Summary Our lab develops and applies integrated experimental and computational methods to elucidate the impact of mechanics on biology at multiple scales. Our goal for the next few years is to uncover how the interplay of complex biophysical factors in the tissue microenvironment drives structural and functional state transitions at the cytoskeletal, cellular, and tissue levels. In particular, we will focus on the interplay between osmotic pressure, extracellular matrix (ECM) crosslinking, and mesoscale ECM architectures. These factors are prominent in tissues and often simultaneously present, but their fundamental integrated impact on cellular systems is not well understood. We will investigate how together they act as inputs that program local molecular and cellular interactions. We will extract the critical input parameter values that induce drastic mode switching, especially in cytoskeletal organization and function, cell migration, cell-matrix interactions, and collective cell dissemination. We will determine the mechanisms and consequences of biophysical transitions at different scales and how they function as on and off switches for global tissue phenotypes.

项目摘要 我们的实验室开发并应用综合实验和计算方法来阐明 力学在生物学上的应用。我们未来几年的目标是揭示 组织微环境中复杂的生物物理因素驱动结构和功能状态的转变， 细胞骨架、细胞和组织水平。特别是，我们将集中在渗透压， 细胞外基质（ECM）交联和中尺度ECM结构。这些因素突出表现在 组织，并经常同时存在，但它们对细胞系统的基本综合影响并不好 明白我们将研究它们如何一起作为输入， 交互.我们将提取引起剧烈模式切换的关键输入参数值，特别是在 细胞骨架组织和功能、细胞迁移、细胞-基质相互作用和集体细胞散布。 我们将确定在不同尺度上生物物理转变的机制和后果，以及它们如何 作为整体组织表型的开关。