An Adhesion-Dependent Switch between Mechanisms That Determine Motile Cell Shape

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（Keratocytes）是一类运动快速的细胞，其黏附动力学与驱动细胞迁移的肌动蛋白聚合马达紧密耦联，进而实现高度协调的细胞运动。本研究发现，改变基底底物的黏附特性会对角膜细胞形态产生显著影响。在中等黏附强度底物上爬行的细胞呈现典型角膜细胞特征：具有宽大的扇形板状伪足（lamellipodium），边界清晰的前缘与后缘，且伸出与回缩速率稳定。低黏附强度底物上的细胞体积小巧且呈圆形，伸出与回缩速率波动极大；高黏附强度底物上的细胞则体积庞大、形态不对称，尤为引人注目的是，其细胞伸出过程呈现出行波现象。为阐明黏附强度调控细胞行为的具体机制，我们对在不同黏附强度底物上迁移的角膜细胞的黏附结构、肌球蛋白II（myosin II）及肌动蛋白网络的组织形式进行了分析。总体而言，本研究结果与一项定量物理模型相符：角膜细胞的形态与迁移行为源自肌动蛋白、黏附结构及肌球蛋白的自组织过程，而黏附强度或肌球蛋白收缩的定量变化，可使角膜细胞在性质迥异的多种迁移模式之间发生切换。