Palecek S P, Horwitz A F, Lauffenburger D A
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, USA.
Ann Biomed Eng. 1999 Mar-Apr;27(2):219-35. doi: 10.1114/1.176.
Under many circumstances, cell migration speed is limited by the rate of cell-substratum detachment at the cell rear. We have constructed a mathematical model to integrate how the biophysical and biochemical interactions between integrins, the cytoskeleton, and the matrix affect rear retraction and linkage dissociation mechanisms. Our model also examines how applied forces and integrin clustering affect retraction kinetics. The model predicts two distinct detachment phenotypes. In the first, detachment is extremely rapid, dominated by integrin extracellular-matrix dissociation, and it occurs at high forces or low adhesiveness. In the second, detachment is much slower, dominated by integrin-cytoskeleton dissociation, and it occurs at low forces or high adhesiveness. The amount of integrin extracted from the rear of the cell is an assay for the detachment phenotype. During rapid detachment cells leave little integrin on the substratum whereas during slow detachment a large fraction of integrin rips from the membrane. This model delineates parameters which can be exploited to regulate cell speed in each detachment regime. The model also offers an explanation as to why some cell types, such as leukocytes or keratocytes, are able to detach easily and move very quickly while other cell types, such as fibroblasts, tend to migrate more slowly and release many more integrins during detachment.
在许多情况下，细胞迁移速度受细胞尾部与基质分离速率的限制。我们构建了一个数学模型，以整合整合素、细胞骨架和基质之间的生物物理和生化相互作用如何影响尾部回缩和连接解离机制。我们的模型还研究了外力和整合素聚集如何影响回缩动力学。该模型预测了两种不同的分离表型。第一种，分离极其迅速，由整合素与细胞外基质的解离主导，发生在高外力或低黏附性条件下。第二种，分离要慢得多，由整合素与细胞骨架的解离主导，发生在低外力或高黏附性条件下。从细胞尾部提取的整合素数量是分离表型的一种检测方法。在快速分离过程中，细胞在基质上留下的整合素很少，而在缓慢分离过程中，很大一部分整合素从膜上撕裂下来。该模型描绘了可用于在每种分离状态下调节细胞速度的参数。该模型还解释了为什么某些细胞类型，如白细胞或角膜细胞，能够轻松分离并快速移动，而其他细胞类型，如成纤维细胞，往往迁移得更慢，并且在分离过程中释放更多的整合素。
