Human fibroblast migration in three-dimensional collagen gel in response to noninvasive electrical stimulus. II. Identification of electrocoupling molecular mechanisms.
Human fibroblast migration in three-dimensional collagen gel in response to noninvasive electrical stimulus. II. Identification of electrocoupling molecular mechanisms.
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DOI：
10.1089/ten.2004.10.1558
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发表时间：
2004-11
影响因子：
--
通讯作者：
Shan Sun;M. Cho
中科院分区：
文献类型：
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作者：
Shan Sun;M. Cho
细胞粘附和迁移是由一系列相互协调、相互整合的分子机制调控的。在随附的文章中（Sun等人，10，1548，2004），我们证明并表征了由非侵入性电刺激诱导的人成纤维细胞在三维（3D）胶原凝胶中的运动。然而，介导三维细胞迁移的分子机制在响应物理刺激，包括非侵入性电刺激仍有待阐明。在这里，我们报告，诱导人成纤维细胞的运动在三维胶原蛋白凝胶是整合素和Ca 2+依赖。用抗整联蛋白抗体处理细胞可防止电诱导的细胞运动。更有趣的是，虽然细胞外Ca 2+的缺乏抑制细胞运动，但细胞表面受体偶联磷脂酶C（PLC）的抑制完全阻止了3D细胞迁移，表明整合素，PLC和细胞内Ca 2+之间的分子关联。耦合外部电刺激PLC激活似乎是诱导细胞迁移所需的主要事件，而跨质膜的Ca 2+内流调节持续的细胞运动。在本研究中使用的电刺激的相当小的强度（0.1 V/cm）的基础上，电操作的电压门控Ca 2+通道的激活是不太可能的，但机械操作的拉伸激活的阳离子通道似乎介导Ca 2+内流。阐明参与三维细胞运动的电偶联分子机制可能会导致三维细胞粘附和迁移的控制和设计操作。
Cell adhesion and migration is regulated by a series of coordinated and integrated molecular mechanisms. In the accompanying article (Sun et al., Tissue Eng. 10, 1548, 2004), we demonstrate and characterize the human fibroblast movement in three-dimensional (3D) collagen gel induced by non-invasive electrical stimulus. The molecular mechanisms mediating 3D cell migration in response to physical stimuli including noninvasive electrical stimulus remain to be elucidated, however. Here we report that induced human fibroblast movement in 3D collagen gel is both integrin and Ca2+ dependent. Treatment of cells with anti-integrin antibodies prevents electrically induced cell movement. More interestingly, whereas the absence of extracellular Ca2+ suppresses cell movement, inhibition of the cell surface receptor-coupled phospholipase C (PLC) completely prevents 3D cell migration, suggesting molecular association between integrin, PLC, and intracellular Ca2+. Coupling of external electrical stimulus to PLC activation appears to be the primary event required to induce cell migration, while Ca2+ influx across the plasma membrane regulates the sustained cell movement. On the basis of the rather small strength (0.1 V/cm) of electrical stimulus used in this study, activation of the electrically operated voltage-gated Ca2+ channels is unlikely, but the mechanically operated stretch-activated cation channels appear to mediate Ca2+ influx. Elucidation of the electrocoupling molecular mechanisms involved in 3D cell movement could lead to controlled and designed manipulation of 3D cell adhesion and migration.