Department of Biochemistry and Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, California, United States of America.
PLoS Biol. 2011 May;9(5):e1001059. doi: 10.1371/journal.pbio.1001059. Epub 2011 May 3.
Keratocytes are fast-moving cells in which adhesion dynamics are tightly coupled to the actin polymerization motor that drives migration, resulting in highly coordinated cell movement. We have found that modifying the adhesive properties of the underlying substrate has a dramatic effect on keratocyte morphology. Cells crawling at intermediate adhesion strengths resembled stereotypical keratocytes, characterized by a broad, fan-shaped lamellipodium, clearly defined leading and trailing edges, and persistent rates of protrusion and retraction. Cells at low adhesion strength were small and round with highly variable protrusion and retraction rates, and cells at high adhesion strength were large and asymmetrical and, strikingly, exhibited traveling waves of protrusion. To elucidate the mechanisms by which adhesion strength determines cell behavior, we examined the organization of adhesions, myosin II, and the actin network in keratocytes migrating on substrates with different adhesion strengths. On the whole, our results are consistent with a quantitative physical model in which keratocyte shape and migratory behavior emerge from the self-organization of actin, adhesions, and myosin, and quantitative changes in either adhesion strength or myosin contraction can switch keratocytes among qualitatively distinct migration regimes.
角膜细胞是运动速度很快的细胞，其黏附动力学与驱动迁移的肌动蛋白聚合马达紧密偶联，导致细胞运动高度协调。我们发现，改变基底的黏附特性对角膜细胞的形态有显著影响。在中等黏附强度下爬行的细胞类似于典型的角膜细胞，其特征是宽的扇形片状伪足，清晰的前缘和后缘，以及持续的突起和缩回速率。在低黏附强度下的细胞较小且呈圆形，突起和缩回速率变化很大，而在高黏附强度下的细胞较大且不对称，并且令人惊讶的是，它们表现出突起的行进波。为了阐明黏附强度决定细胞行为的机制，我们研究了在具有不同黏附强度的基底上迁移的角膜细胞中黏附、肌球蛋白 II 和肌动蛋白网络的组织。总的来说，我们的结果与一个定量物理模型一致，即角膜细胞的形状和迁移行为源自肌动蛋白、黏附物和肌球蛋白的自组织，黏附强度或肌球蛋白收缩的定量变化可以使角膜细胞在不同的迁移状态之间切换。
