Palecek S P, Loftus J C, Ginsberg M H, Lauffenburger D A, Horwitz A F
Department of Chemical Engineering and Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge 02139, USA.
Nature. 1997 Feb 6;385(6616):537-40. doi: 10.1038/385537a0.
Migration of cells in higher organisms is mediated by adhesion receptors, such as integrins, that link the cell to extracellular-matrix ligands, transmitting forces and signals necessary for locomotion. Whether cells will migrate or not on a given substratum, and also their speed, depends on several variables related to integrin-ligand interactions, including ligand levels, integrin levels, and integrin-ligand binding affinities. These and other factors affect the way molecular systems integrate to effect and regulate cell migration. Here we show that changes in cell migration speed resulting from three separate variables-substratum ligand level, cell integrin expression level, and integrin-ligand binding affinity-are all quantitatively predictable through the changes they cause in a single unifying parameter: short-term cell-substratum adhesion strength. This finding is consistent with predictions of a mathematical model for cell migration. The ligand concentration promoting maximum migration speed decreases reciprocally as integrin expression increases. Increases in integrin-ligand affinity similarly result in maximal migration at reciprocally lower ligand concentrations. The maximum speed attainable, however, remains unchanged as ligand concentration, integrin expression, or integrin-ligand affinity vary, suggesting that integrin coupling with intracellular motors remains unaltered.
高等生物中细胞的迁移由黏附受体介导，如整合素，它将细胞与细胞外基质配体相连，传递运动所需的力和信号。细胞在给定基质上是否会迁移以及迁移速度，取决于与整合素 - 配体相互作用相关的几个变量，包括配体水平、整合素水平和整合素 - 配体结合亲和力。这些因素以及其他因素会影响分子系统整合以实现和调节细胞迁移的方式。在这里，我们表明，由三个独立变量——基质配体水平、细胞整合素表达水平和整合素 - 配体结合亲和力——引起的细胞迁移速度变化，都可以通过它们在一个统一参数中引起的变化进行定量预测：短期细胞 - 基质黏附强度。这一发现与细胞迁移数学模型的预测一致。随着整合素表达增加，促进最大迁移速度的配体浓度呈反比下降。整合素 - 配体亲和力的增加同样会在反比更低的配体浓度下导致最大迁移。然而，随着配体浓度、整合素表达或整合素 - 配体亲和力的变化，可达到的最大速度保持不变，这表明整合素与细胞内马达的耦合保持不变。
