James Jane, Goluch Edgar D, Hu Huan, Liu Chang, Mrksich Milan
Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois, USA.
Cell Motil Cytoskeleton. 2008 Nov;65(11):841-52. doi: 10.1002/cm.20305.
This paper employs substrates that are patterned with shapes having well-defined geometric cues to characterize the influence of curvature on the polarization of highly metastatic B16F10 rat melanoma cells. Substrates were patterned using microcontact printing to define adhesive islands of defined shape and size on a background that otherwise prevents cell adhesion. Cells adherent to these surfaces responded to local curvature at the perimeter of the adhesive islands; convex features promoted the assembly of lamellipodia and concave features promoted the assembly of stress filaments. Cells adherent to rectangular shapes displayed a polarized cytoskeleton that increased with the aspect ratio of the shapes. Shapes that combined local geometric cues, by way of concave or convex edges, with aspect ratio were used to understand the additive effects of shape on polarization. The dependence of cell polarity on shape was determined in the presence of small molecules that alter actomyosin contractility and revealed a stronger dependence on contractility for shapes having straight edges, in contrast to those having curved edges. This study demonstrates that the cytoskeleton modulates cell polarity in response to multiple geometric cues in the extracellular environment.
本文采用具有明确几何线索形状的图案化基质,以表征曲率对高转移性B16F10大鼠黑色素瘤细胞极化的影响。使用微接触印刷对基质进行图案化,以在否则会阻止细胞粘附的背景上定义具有确定形状和大小的粘附岛。附着在这些表面上的细胞对粘附岛周边的局部曲率做出反应;凸起特征促进片状伪足的组装,而凹陷特征促进应力丝的组装。附着在矩形上的细胞显示出极化的细胞骨架,其随着形状的长宽比增加。通过凹边或凸边将局部几何线索与长宽比相结合的形状用于理解形状对极化的累加效应。在存在改变肌动球蛋白收缩性的小分子的情况下,确定了细胞极性对形状的依赖性,结果表明,与具有弯曲边缘的形状相比,具有直边缘的形状对收缩性的依赖性更强。这项研究表明,细胞骨架会响应细胞外环境中的多种几何线索来调节细胞极性。