Cell Traction Forces Direct Fibronectin Matrix Assembly
Cell Traction Forces Direct Fibronectin Matrix Assembly
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DOI：
10.1016/j.bpj.2008.10.009
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发表时间：
2009-01-21
影响因子：
3.4
通讯作者：
Romer, Lewis H.
中科院分区：
文献类型：
--
作者：
Lemmon, Christopher A.;Chen, Christopher S.;Romer, Lewis H.
细胞与周围基质之间的相互作用对于组织的发育和工程至关重要。我们研究了细胞衍生的牵引力在细胞外基质组装中的作用，我们认为这是一种新颖的测定方法，可以同时测量离散细胞基质附着位点的牵引力和纤连蛋白原纤维的生长。将 NIH3T3 细胞铺在可变形悬臂柱阵列上 2-24 小时。数据表明，发育中的原纤维方向是由施加到该原纤维的牵引力的方向引导的。此外，细胞最初建立牵引力的空间分布，该分布在细胞边缘处最大，并向细胞中心减小。随着细胞周边的压缩应变随着时间的推移而减小，这种分布逐渐从主要的外围模式转变为更均匀的模式。通过用 blebbistatin 或 calyculin A 处理细胞以分别强效阻断或增强肌球蛋白 II 活性来测试这些变化对原纤维形成的影响。随着时间的推移，两种治疗方法都阻止了牵引力的向内转移、压缩应变的消散和纤连蛋白原纤维的形成。这些数据表明牵引力和局部应变的动态空间和时间变化可能有助于成功的矩阵组装。
Interactions between cells and the surrounding matrix are critical to the development and engineering of tissues. We have investigated the role of cell-derived traction forces in the assembly of extracellular matrix using what we believe is a novel assay that allows for simultaneous measurement of traction forces and fibronectin fibril growth at discrete cell-matrix attachment sites. NIH3T3 cells were plated onto arrays of deformable cantilever posts for 2-24 h. Data indicate that developing fibril orientation is guided by the direction of the traction force applied to that fibril. In addition, cells initially establish a spatial distribution of traction forces that is largest at the cell edge and decreases toward the cell center. This distribution progressively shifts from a predominantly peripheral pattern to a more uniform pattern as compressive strain at the cell perimeter decreases with time. The impact of these changes on fibrillogenesis was tested by treating cells with blebbistatin or calyculin A to tonically block or augment, respectively, myosin II activity. Both treatments blocked the inward translation of traction forces, the dissipation of compressive strain, and fibronectin fibrillogenesis overtime. These data indicate that dynamic spatial and temporal changes in traction force and local strain may contribute to successful matrix assembly.