Fibroblast‐populated collagen microsphere assay of cell traction force: Part 1. Continuum model
Fibroblast‐populated collagen microsphere assay of cell traction force: Part 1. Continuum model
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成纤维细胞填充的胶原微球细胞牵引力测定：第 1 部分：连续体模型
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发表时间：
1993
期刊：
影响因子：
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通讯作者：
R. Tranquillo
中科院分区：
文献类型：
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作者：
Alice G. Moon;R. Tranquillo
目前用于表征细胞外基质 (ECM) 纤维上施加的细胞牵引力的最流行的体外测定是成纤维细胞填充的胶原蛋白晶格 (FPCL) 测定。细胞填充的胶原凝胶盘的压实，以直径减小的速率或程度而言，通常被报告为细胞牵引的量度。然而，该测量取决于固有牵引力附带的测定特性，例如初始细胞浓度、初始胶原蛋白浓度和凝胶的几何形状。因此，显然需要识别和测量细胞牵引的客观指标。在这里，我们提出了在连续介质理论中定义的牵引参数（反映细胞-纤维机械相互作用）作为这样的指数，其中细胞运动和 ECM 变形的交互过程通过与细胞-ECM 复合材料的机械力平衡耦合的细胞和 ECM 守恒表达式进行建模。这些方程是为我们对 FPCL 测定的适应而制定和求解的，其中细胞最初分散在胶原凝胶微球中，与流行的圆盘几何形状相比，具有一些实验和理论优势。然后将偏微分方程非线性系统的解（根据牵引参数进行参数化）与成纤维细胞填充的胶原微球 (FPCM) 的压实数据进行比较。我们表明，当初始细胞浓度和初始 FPCM 直径变化时，模型预测与数据一致。在第 2 部分中，我们展示了这些结果以及细胞生长参数和凝胶粘弹性参数的确定如何使我们能够估计牵引参数的大小，这是对生理相关胶原凝胶中成纤维细胞施加的牵引力的直接测量。
The most popular in vitro assay currently used to characterize cell traction forces exerted on extracellular matrix (ECM) fibers is the fibroblast-populated collagen lattice (FPCL) assay. The compaction of a disk of cell-populated collagen gel, in terms of rate or extent of diameter reduction, is typically reported as the measure of cell traction. This measure, however, depends on assay properties incidental to the intrinsic traction, such as the initial cell concentration, the initial collagen concentration, and the geometry of the gel. Thus, there is a clear need to identify and measure an objective index of cell traction. Here, we propose as such an index a traction parameter (reflective of the cell-fiber mechanical interaction) defined in a continuum theory in which the interactive processes of cell motility and ECM deformation are modeled by expressions for cell and ECM conservation coupled to the mechanical force balance for the cell-ECM composite. The equations are formulated and solved for our adaptation of the FPCL assay in which cells are initially dispersed in a collagen gel microsphere, conferring several experimental and theoretical advantages over the popular disk geometry. The solution of the nonlinear system of partial differential equations (parameterized on the traction parameter) is then compared to compaction data for the fibroblast-populated collagen microspheres (FPCM). We show that the model predictions are consistent with the data when the initial cell concentration and the initial FPCM diameter are varied. In Part 2, we show how these results, along with the determination of the growth parameters of the cells and the viscoelastic parameters of the gel, have allowed us to estimate the magnitude of the traction parameter, which is a direct measure of the traction exerted by fibroblasts in a physiologically relevant collagen gel.