Dynamic Formation for the Mechanical Connection of Focal Adhesion Complexes to Study Localized Mechanisms of Angiogenesis Through Modeling With Cellular Automata

P. Leduc
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Abstract

The mechanical connection through the formation of focal adhesion complexes (FACs) is critical in cell growth and apoptosis. The FACs act between the cells and the extracellular matrix (ECM), which in turn influences angiogenesis, the growth of new capillary blood vessels [1]. These complexes form direct connections from ECM into the cell cytoskeleton through a series of protein binding events. This linkage is critical for mechanical force sensing and mechanotransduction signaling [2]. Here, the probabilistic modeling of this complex formation is undertaken to begin to uncover the effect of the spatial distribution and temporal effects on this dynamic process. In this, the rich dynamic process of the FACs formation through the binding events of integrin, paxillin, talin, and vinculin are examined. The FACs are mediated through the clustering of transmembrane integrins, which initiate the binding cascade. This interaction has been shown to be a critical event in the activation of the mechanochemical cascade and further mediates downstream signaling of protein tyrosine kinases including focal adhesion kinase [3].
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通过元胞自动机模型研究局部血管生成机制:局部黏附复合物机械连接的动态形成
通过形成局灶黏附复合物(FACs)的机械连接在细胞生长和凋亡中是至关重要的。FACs作用于细胞和细胞外基质(ECM)之间,进而影响血管生成,即新毛细血管的生长[1]。这些复合物通过一系列蛋白质结合事件从ECM到细胞骨架形成直接连接。这种联系对于机械力传感和机械转导信号传导至关重要[2]。在这里,对这一复杂地层进行概率建模,开始揭示空间分布和时间效应对这一动态过程的影响。通过整合素、帕罗西林、talin和长春素的结合事件,研究了FACs形成的丰富动态过程。FACs是通过跨膜整合素的聚集介导的,它启动了结合级联。这种相互作用已被证明是机械化学级联激活的关键事件,并进一步介导包括局灶黏附激酶在内的蛋白酪氨酸激酶的下游信号传导[3]。
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