Azatov Mikheil, Sun Xiaoyu, Suberi Alexandra, Fourkas John T, Upadhyaya Arpita
Department of Physics, University of Maryland, College Park, MD 20742, United States of America.
Phys Biol. 2017 Nov 3;14(6):065003. doi: 10.1088/1478-3975/aa7acc.
Cells can sense and adapt to mechanical properties of their environment. The local geometry of the extracellular matrix, such as its topography, has been shown to modulate cell morphology, migration, and proliferation. Here we investigate the effect of micro/nanotopography on the morphology and cytoskeletal dynamics of human pancreatic tumor-associated fibroblast cells (TAFs). We use arrays of parallel nanoridges with variable spacings on a subcellular scale to investigate the response of TAFs to the topography of their environment. We find that cell shape and stress fiber organization both align along the direction of the nanoridges. Our analysis reveals a strong bimodal relationship between the degree of alignment and the spacing of the nanoridges. Furthermore, focal adhesions align along ridges and form preferentially on top of the ridges. Tracking actin stress fiber movement reveals enhanced dynamics of stress fibers on topographically patterned surfaces. We find that components of the actin cytoskeleton move preferentially along the ridges with a significantly higher velocity along the ridges than on a flat surface. Our results suggest that a complex interplay between the actin cytoskeleton and focal adhesions coordinates the cellular response to micro/nanotopography.
细胞能够感知并适应其周围环境的力学特性。细胞外基质的局部几何结构，如表面形貌，已被证明可调节细胞形态、迁移和增殖。在此，我们研究了微/纳米形貌对人胰腺肿瘤相关成纤维细胞（TAFs）形态和细胞骨架动力学的影响。我们使用亚细胞尺度上具有可变间距的平行纳米脊阵列，来研究TAFs对其周围环境形貌的反应。我们发现细胞形状和应力纤维组织都沿着纳米脊的方向排列。我们的分析揭示了排列程度与纳米脊间距之间存在很强的双峰关系。此外，粘着斑沿着脊排列并优先在脊的顶部形成。追踪肌动蛋白应力纤维的运动发现，在具有形貌图案的表面上应力纤维的动力学增强。我们发现肌动蛋白细胞骨架的组成部分优先沿着脊移动，沿着脊移动的速度明显高于在平坦表面上的速度。我们的结果表明，肌动蛋白细胞骨架和粘着斑之间的复杂相互作用协调了细胞对微/纳米形貌的反应。
