Distinct roles of frontal and rear cell-substrate adhesions in fibroblast migration
Distinct roles of frontal and rear cell-substrate adhesions in fibroblast migration
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DOI：
10.1091/mbc.12.12.3947
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发表时间：
2001-12-01
影响因子：
3.3
通讯作者：
Dembo, M
中科院分区：
文献类型：
--
作者：
Munevar, S;Wang, YL;Dembo, M
细胞迁移涉及与基质的复杂物理和化学相互作用。为了探测迁移3 T3成纤维细胞不同区域下的机械相互作用，我们通过局部应用GRGDTP肽破坏了细胞-基质粘附，同时用牵引力显微镜对基质上的应力分布进行成像。自发和GRGDTP诱导的后缘脱离引起广泛的细胞缩短，而不改变牵引力的整体水平或迁移的方向。相比之下，在细胞发生任何显著缩短之前，额叶粘连的破坏导致牵引力的显著、全局性损失。虽然牵引力和细胞迁移恢复10-20分钟内短暂的正面治疗，持续治疗GRGDTP引起的细胞发展牵引力的其他地方，并重新定位到一个新的方向。我们的结论是成纤维细胞的收缩力通过两种不同类型的粘连传递到基板。前缘粘连在其传递主动推进力的能力方面是独特的。它们的功能在分离时不能直接转移到现有的粘连上。尾端粘连在细胞迁移过程中产生被动阻力，并在分离时容易重新分配其负荷。我们的研究结果表明，不同的性质的机械相互作用的领先与落后的边缘，共同产生的机械相互作用成纤维细胞迁移。
Cell migration involves complex physical and chemical interactions with the substrate. To probe the mechanical interactions under different regions of migrating 3T3 fibroblasts, we have disrupted cell-substrate adhesions by local application of the GRGDTP peptide, while imaging stress distribution on the substrate with traction force microscopy. Both spontaneous and GRGDTP-induced detachment of the trailing edge caused extensive cell shortening, without changing the overall level of traction forces or the direction of migration. In contrast, disruption of frontal adhesions caused dramatic, global loss of traction forces before any significant shortening of the cell. Although traction forces and cell migration recovered within 10-20 min of transient frontal treatment, persistent treatment with GRGDTP caused the cell to develop traction forces elsewhere and reorient toward a new direction. We conclude that contractile forces of a fibroblast are transmitted to the substrate through two distinct types of adhesions. Leading edge adhesions are unique in their ability to transmit active propulsive forces. Their functions cannot be transferred directly to existing adhesions upon detachment. Trailing end adhesions create passive resistance during cell migration and readily redistribute their loads upon detachment. Our results indicate the distinct nature of mechanical interactions at the leading versus trailing edges, which together generate the mechanical interactions for fibroblast migration.