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:10245019
- 负责人:
- 金额:$ 42.57万
- 依托单位:
- 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:
- 关键词:3-DimensionalActinsActomyosinAddressAffectBehaviorBindingBiologicalBiological ProcessBiomechanicsBiomimeticsBiopolymersBlood capillariesCell CommunicationCell ShapeCell membraneCell modelCellsChemicalsCollagenCommunicationComplexComputer ModelsConsumptionCoupledCytokinesisCytoskeletonDevelopmentDiseaseDistantEquilibriumExperimental ModelsExtracellular MatrixF-ActinFeedbackGenerationsGrainHumanIn VitroKnowledgeLeadLengthLightMechanicsMembraneMicrofilamentsMissionModelingMolecular MotorsMorphogenesisMorphologyMotorMuscleMuscle CellsMyosin ATPaseNeoplasm MetastasisOsmotic PressureOutcomePathogenesisPhysicsPhysiologicalPlayProcessPropertyProteinsRelaxationResearchResearch PersonnelRheologyRoleShapesStressStructureStructure of thyroid parafollicular cellStudy modelsSystemTalentsTissuesTranslatingUnited States National Institutes of HealthVascular DiseasesWalkingbasebiological systemsbiophysical propertiescell motilitycell transformationdisabilityexperienceexperimental studyextracellularfield studyin vitro Assayin vivoinsightmechanical forcemulti-scale modelingnovelnovel therapeutic interventionsimulationspatiotemporaltheoriestransmission processviscoelasticitywound 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-肌动蛋白之间的分子相互作用
以及细胞骨架中的肌球蛋白分子马达。在细胞骨架水平产生的力被转化为
细胞和组织尺度,促进有趣的生物力学现象在多个尺度。例如它
赋予肌动蛋白细胞骨架复杂的、非平衡的粘弹性,
基于热平衡的统计物理学理论。它还推动了剧烈的形态学变化,
在细胞迁移、分裂和增殖中伴随细胞骨架大规模流动的细胞转化,
形态发生此外,细胞利用细胞骨架产生的力进行结构重塑
以及用于在伤口愈合中与其它细胞机械连通
和毛细血管形态发生。在所有这些生物力学现象中,
生成,传输和放松起着非常重要的作用,平衡的破坏
对疾病的发病机制,如癌症转移,产生巨大影响。尽管重要的是
机械力,对调节生物结构中微妙平衡的原理的理解,
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
阐明力的产生、传递和松弛的普遍作用和基本原理,
在细胞骨架、细胞和组织尺度上的生物过程。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在混乱的肌动蛋白细胞骨架
以及ii)这些力如何转化为细胞和组织尺度并调节细胞形状变化,
通过与其他细胞的相互作用和竞争,
细胞内和细胞外因子。拟议研究的结果将为以下方面提供重要见解:
对由机械力调节的生理和病理生理过程有基本的了解。
1
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Taeyoon Kim其他文献
Taeyoon Kim的其他文献
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{{ truncateString('Taeyoon Kim', 18)}}的其他基金
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
- 批准号:
10388935 - 财政年份:2017
- 资助金额:
$ 42.57万 - 项目类别:
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
- 批准号:
9427516 - 财政年份:2017
- 资助金额:
$ 42.57万 - 项目类别:
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
- 批准号:
10001072 - 财政年份:2017
- 资助金额:
$ 42.57万 - 项目类别:
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STRUCTURE/INTERACTIONS OF ACTINS AND ACTIN-BINDING PROTEIN
肌动蛋白和肌动蛋白结合蛋白的结构/相互作用
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