权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
10388935
负责人：
Taeyoon Kim
金额：
$ 10万
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 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10388935
关键词：
3-Dimensional Actins Actomyosin Address Affect Behavior Binding Biological Biological Process Biomechanics Biomimetics Biopolymers Blood capillaries Cell Communication Cell Shape Cell membrane Cell model Cells Chemicals Collagen Communication Complex Computer Models Consumption Coupled Cytokinesis Cytoskeleton Development Disease Distant Equilibrium Experimental Models Extracellular Matrix F-Actin Feedback Generations Grain 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 base biological systems biophysical properties 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 wound healing

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-之间的分子相互作用。肌动蛋白和肌球蛋白分子马达在细胞骨架。在细胞骨架水平产生的力是转化为细胞和组织尺度，促进有趣的生物力学现象在多个尺度。为例如，它赋予肌动蛋白细胞骨架复杂的非平衡粘弹性，可以用基于热平衡的统计物理学理论来描述。它也会导致剧烈的细胞形态的转变伴随着细胞骨架在细胞中的大规模流动迁移、分裂和形态发生。此外，细胞利用细胞骨架产生的力在结构上重塑周围的细胞外基质以及用于与其他细胞在伤口愈合和毛细血管形态发生中的作用。在所有这些生物力学现象中，力的产生、传递和松弛之间的平衡起着非常重要的作用，这种平衡对疾病的发病机制，如癌症转移，有着巨大的影响。尽管机械力的意义，对调节生物学中微妙平衡的原理的理解结构仍然缺乏。通过开发多尺度计算模型和采用定量体外实验，我们将阐明普遍的作用和基本原则的力量产生，传输，以及在细胞骨架、细胞和组织尺度上的生物过程中的松弛。我们的目标是解决两个基本问题：i）力是如何产生的，并导致非平衡粘弹性行为，混乱的肌动蛋白细胞骨架和ii）如何将力转化为细胞和组织尺度并调节细胞形状变化，基质重塑，以及通过相互作用在远处细胞之间进行机械通信并与其他细胞内和细胞外因子竞争。拟议研究的成果将提供对生理和病理生理过程的基本理解的重要见解由机械力调节。 1

项目成果

期刊论文数量（32）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

In Vitro Reconstitution of the Actin Cytoskeleton Inside Giant Unilamellar Vesicles.

巨型单层囊泡内肌动蛋白细胞骨架的体外重建。

DOI：
10.3791/64026
发表时间：
2022
期刊：
Journal of visualized experiments : JoVE
影响因子：
0
作者：
Chen,Sheng;Sun,ZacharyGao;Murrell,MichaelP
通讯作者：
Murrell,MichaelP

Emergence of diverse patterns driven by molecular motors in the motility assay.

运动测定中分子马达驱动的多种模式的出现。

DOI：
10.1002/cm.21808
发表时间：
2023
期刊：
Cytoskeleton (Hoboken, N.J.)
影响因子：
0
作者：
Slater,Brandon;Jung,Wonyeong;Kim,Taeyoon
通讯作者：
Kim,Taeyoon

Weak catch bonds make strong networks.

DOI：
10.1038/s41563-022-01288-0
发表时间：
2022-09
期刊：
Nature materials
影响因子：
41.2
作者：
Mulla Y;Avellaneda MJ;Roland A;Baldauf L;Jung W;Kim T;Tans SJ;Koenderink GH
通讯作者：
Koenderink GH

Role of actin filaments and cis binding in cadherin clustering and patterning.

肌动蛋白丝和顺式结合在钙粘蛋白聚类和图案中的作用。

DOI：
10.1371/journal.pcbi.1010257
发表时间：
2022-07
期刊：
PLoS computational biology
影响因子：
4.3
作者：
通讯作者：

Entropy production rate is maximized in non-contractile actomyosin.

非收缩性肌动球蛋白的熵产生率最大化。

DOI：
10.1038/s41467-018-07413-5
发表时间：
2018
期刊：
Nature communications
影响因子：
16.6
作者：
Seara,DanielS;Yadav,Vikrant;Linsmeier,Ian;Tabatabai,APasha;Oakes,PatrickW;Tabei,SMAli;Banerjee,Shiladitya;Murrell,MichaelP
通讯作者：
Murrell,MichaelP