Universal Roles of Force Generation and Transmission in Biological Systems

生物系统中力的产生和传递的普遍作用

基本信息

批准号：
9427516
负责人：
Taeyoon Kim
金额：
$ 45.67万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9427516
关键词：
Actins Actomyosin Address Affect Alpha Cell Behavior Binding Biological Biological Process Biomechanics Biomimetics Biopolymers Blood capillaries Cell Communication Cell Shape Cell membrane Cell model Cells Cereals Chemicals Collagen Communication Complex Computer Simulation Coupled Cytokinesis Cytoskeleton Development Dimensions Disease Distant Equilibrium Experimental Models Extracellular Matrix F-Actin Feedback Generations Human In Vitro Knowledge Lead Length Light Mechanics Membrane Microfilaments Mission Modeling Molecular Motors Morphogenesis Morphology Motor Muscle Muscle Cells Myosin ATPase Neoplasm Metastasis Osmotic Pressure Outcome Pathogenesis Physics Physiological Play Process Property Proteins Relaxation Research Research Personnel Rheology Role Shapes Stress Structure Structure of thyroid parafollicular cell Study models System Talents Tissues Translating United States National Institutes of Health Vascular Diseases Walking Wound Healing base biological systems biophysical properties capillary cell motility cell transformation disability experience experimental study extracellular field study in vitro Assay in vivo insight mechanical force multi-scale modeling novel novel therapeutic intervention simulation spatiotemporal theories transmission process viscoelasticity

项目摘要

PROJECT SUMMARY The ability of cells to generate mechanical forces is attributed primarily to molecular interactions between F-actin and myosin molecular motors in the cell cytoskeleton. Force generated at the cytoskeleton level is translated to cellular and tissue scales, facilitating interesting biomechanical phenomena at multiple scales. For example, it endows the actin cytoskeleton with complex, non-equilibrium viscoelastic properties which cannot be described by theories from statistical physics based on thermal equilibrium. It also drives drastic morphological transformations of cells accompanied by large-scale flow of the cell cytoskeleton in cell migration, division, and morphogenesis. In addition, cells use the force produced from the cytoskeleton for structurally remodeling surrounding extracellular matrices as well as for mechanically communicating with other cells in wound healing and capillary morphogenesis. In all these biomechanical phenomena, a delicate balance between force generation, transmission, and relaxation plays a very important role, and the disruption of the balance has dramatic impacts on the pathogenesis of disease, such as cancer metastasis. Despite the significance of mechanical forces, understanding of principles that regulate the delicate balance in biological structures still lacks. By developing multi-scale computational models and employing quantitative in vitro experiments, we will shed light on universal roles and underlying principles of force generation, transmission, and relaxation in biological processes at cytoskeleton, cell, and tissue scales. We aim to address two fundamental questions: i) how forces are generated and lead to non-equilibrium viscoelastic behaviors in disorganized actin cytoskeleton and ii) how the forces are translated to cellular and tissue scales and regulate cell shape changes, matrix remodeling, and mechanical communication between distant cells by interacting and competing with other intracellular and extracellular factors. Outcomes from the proposed research will provide critical insights into fundamental understanding of physiological and pathophysiological processes regulated by mechanical forces. 1

项目摘要细胞产生机械力的能力主要归因于F-肌动蛋白之间的分子相互作用细胞细胞骨架中的肌球蛋白分子电机。在细胞骨架水平上产生的力转化为细胞和组织量表，促进多个尺度上有趣的生物力学现象。例如，它将肌动蛋白细胞骨架具有复杂的，非平衡的粘弹性特性，无法描述通过基于热平衡的统计物理学的理论。它也驱动了刺耳的形态学细胞的转化以及细胞迁移，分裂和形态发生。此外，细胞使用由细胞骨架产生的力进行结构重塑围绕细胞外矩阵以及在伤口愈合中与其他细胞机械通信和毛细血管形态发生。在所有这些生物力学现象中，力量之间的微妙平衡产生，传播和放松起着非常重要的作用，平衡的破坏具有对疾病的发病机理的巨大影响，例如癌症转移。尽管有重要意义机械力，理解调节生物结构中微妙平衡的原理缺乏。通过开发多尺度计算模型并采用定量体外实验，我们将阐明了普遍角色和力量产生，传播和放松的基本原则细胞骨架，细胞和组织尺度的生物过程。我们的目标是解决两个基本问题：i）如何产生力并导致混乱的肌动蛋白细胞骨架中的非平衡粘弹性行为 ii）如何将力转化为细胞和组织尺度并调节细胞形状变化，矩阵通过与其他相互作用和竞争，重塑和远处细胞之间的机械通信细胞内和细胞外因子。拟议研究的结果将为您提供关键见解对由机械力调节的生理和病理生理过程的基本理解。 1