A chemo-mechanical model for growth and mechanosensing of focal adhesion

IF 5 2区 工程技术 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY
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引用次数: 0

Abstract

Focal adhesion (FA), the complex molecular assembly across the lipid membrane, serves as a hub for physical and chemical information exchange between cells and their microenvironment. Interestingly, studies have shown that FAs can grow along the direction of contractile forces generated by actomyosin stress fibers and achieve larger sizes on stiffer substrates. In addition, the cellular traction transmitted to the substrate was observed to reach the maximum near the FA center. However, the biomechanical mechanisms behind these intriguing findings remain unclear. To answer this important question, here we first developed a one-dimensional (1D) chemo-mechanical model of FA where key features like adhesion plaque deformation, active contraction by stress fibers, force-dependent association/dissociation of integrin bonds connecting two surfaces, and substrate compliance have all been considered. Within this formulation, we showed that the rigidity-sensing capability of FAs originates from the deformability of stress fibers while the force-dependent breakage of integrin bonds leads to the appearance of the traction peak at the FA center. Furthermore, by extending the model into three-dimensional as well as incorporating assembly/dis-assembly kinetics of adhesion proteins, we also demonstrated how anisotropic stress/strain field within the adhesion plaque will be induced by the presence of contractile forces which leads to the directional growth of the FA.

病灶粘附生长和机械传感的化学机械模型
病灶粘附(FA)是横跨脂膜的复杂分子组装,是细胞与其微环境之间进行物理和化学信息交流的枢纽。有趣的是,研究表明,FA 可以沿着肌动蛋白应力纤维产生的收缩力方向生长,并在较硬的基质上形成较大的尺寸。此外,还观察到传递到基质的细胞牵引力在 FA 中心附近达到最大值。然而,这些有趣发现背后的生物力学机制仍不清楚。为了回答这一重要问题,我们首先建立了 FA 的一维化学机械模型,其中考虑了粘附斑块变形、应力纤维的主动收缩、连接两个表面的整合素键的力依赖性结合/解离以及基质顺应性等关键特征。在这一表述中,我们发现 FA 的刚度感应能力源于应力纤维的可变形性,而依赖于力的整合素键断裂导致了 FA 中心牵引峰的出现。此外,通过将模型扩展为三维模型并结合粘附蛋白的组装/解组装动力学,我们还证明了粘附斑块内各向异性的应力/应变场是如何由收缩力引起的,从而导致 FA 的定向生长。
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来源期刊
Journal of The Mechanics and Physics of Solids
Journal of The Mechanics and Physics of Solids 物理-材料科学:综合
CiteScore
9.80
自引率
9.40%
发文量
276
审稿时长
52 days
期刊介绍: The aim of Journal of The Mechanics and Physics of Solids is to publish research of the highest quality and of lasting significance on the mechanics of solids. The scope is broad, from fundamental concepts in mechanics to the analysis of novel phenomena and applications. Solids are interpreted broadly to include both hard and soft materials as well as natural and synthetic structures. The approach can be theoretical, experimental or computational.This research activity sits within engineering science and the allied areas of applied mathematics, materials science, bio-mechanics, applied physics, and geophysics. The Journal was founded in 1952 by Rodney Hill, who was its Editor-in-Chief until 1968. The topics of interest to the Journal evolve with developments in the subject but its basic ethos remains the same: to publish research of the highest quality relating to the mechanics of solids. Thus, emphasis is placed on the development of fundamental concepts of mechanics and novel applications of these concepts based on theoretical, experimental or computational approaches, drawing upon the various branches of engineering science and the allied areas within applied mathematics, materials science, structural engineering, applied physics, and geophysics. The main purpose of the Journal is to foster scientific understanding of the processes of deformation and mechanical failure of all solid materials, both technological and natural, and the connections between these processes and their underlying physical mechanisms. In this sense, the content of the Journal should reflect the current state of the discipline in analysis, experimental observation, and numerical simulation. In the interest of achieving this goal, authors are encouraged to consider the significance of their contributions for the field of mechanics and the implications of their results, in addition to describing the details of their work.
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