Effect of actomyosin contractility on lamellipodial protrusion dynamics on a micropatterned substrate
Effect of actomyosin contractility on lamellipodial protrusion dynamics on a micropatterned substrate
复制标题
肌动球蛋白收缩性对微图案基底上片状足突起动力学的影响
DOI：
10.1007/s12195-011-0190-y
复制
发表时间：
2011
影响因子：
2.8
通讯作者：
K.O.Okeyo
中科院分区：
文献类型：
--
作者：
Saito;et al.;福嶋貴・田中晃二;末包文彦;K.O.Okeyo
肌动蛋白聚合驱动的片状脂膜突起是肌动蛋白为基础的细胞迁移过程中必不可少的初始步骤，并与与底物的附着密切相关。尽管近年来在阐明局灶性粘连的分子细节方面取得了巨大的进展，但我们对突起和粘连的基本协调以及这两个基本过程如何与肌球蛋白收缩有关的了解仍然不够。因此，为了突出细胞-底物相互作用对片状脂体突起动力学的影响，并将突起与肌动球蛋白活性联系起来，本研究研究了鱼类表皮角质形成细胞在具有不同宽度的黏附抑制间隙的纤维连接蛋白微图案上的迁移。我们发现，与缝隙相关的粘附力不足可以限制板脂突起，从而使迁移细胞的百分比随着缝隙宽度的增加而减少，并且穿过缝隙的突起伴随着褶皱。此外，我们的结果表明，上调肌动蛋白的收缩能力增强了肌动蛋白细胞骨架的机械完整性，导致片状脂膜的宽度增加，从而增加了细胞跨越缝隙的迁移百分比。因此，我们证明，迁移细胞前沿的突起动力学在功能上参与了使细胞迁移的肌动蛋白细胞骨架组件的全球机械调节。
Actin polymerization-driven protrusion of the lamellipodia is a requisite initial step during actin-based cell migration, and is closely associated with attachment to the substrate. Although tremendous progress has been made in recent years toward elucidating the molecular details of focal adhesions, our understanding of the basic coordination of protrusion and adhesion, and how the two fundamental processes relate to actomyosin contractility is still inadequate. Therefore, to highlight the effect of cell–substrate interactions on the protrusive dynamics of the lamellipodia and to correlate protrusion with actomyosin activities, this study investigated the migration of fish epidermal keratocytes on fibronectin micropatterns intercalated with adhesion-suppressed gaps of varying widths. We show that insufficient adhesion associated with the gaps could limit lamellipodial protrusion such that the percentage of migrating cells decreases with an increase in gap width, and protrusion across the gaps is accompanied by ruffling. Moreover, our results suggest that up-regulating actomyosin contractility enhances the mechanical integrity of the actin cytoskeleton, leading to an increase in the width of the lamellipodia, and consequently, an increase in the percentage of cells migrating across the gaps. Thus, we demonstrate that the protrusion dynamics at the leading edge of migrating cells are functionally involved in the global mechanical regulation of actin cytoskeletal components that enable cell migration.