Tzvetkova-Chevolleau Tzvetelina, Stéphanou Angélique, Fuard David, Ohayon Jacques, Schiavone Patrick, Tracqui Philippe
LTM/CNRS/UMR5129, c/o CEA Grenoble, 17 rue des Martyrs, 38054 Grenoble cedex 9, France.
Biomaterials. 2008 Apr;29(10):1541-51. doi: 10.1016/j.biomaterials.2007.12.016. Epub 2008 Jan 11.
Cell adhesion and migration are strongly influenced by extracellular matrix (ECM) architecture and rigidity, but little is known about the concomitant influence of such environmental signals to cell responses, especially when considering cells of similar origin and morphology, but exhibiting a normal or cancerous phenotype. Using micropatterned polydimethylsiloxane substrates (PDMS) with tunable stiffness (500 kPa, 750 kPa, 2000 kPa) and topography (lines, pillars or unpatterned), we systematically analyse the differential response of normal (3T3) and cancer (SaI/N) fibroblastic cells. Our results demonstrate that both cells exhibit differential morphology and motility responses to changes in substrate rigidity and microtopography. 3T3 polarisation and spreading are influenced by substrate microtopography and rigidity. The cells exhibit a persistent type of migration, which depends on the substrate anisotropy. In contrast, the dynamic of SaI/N spreading is strongly modified by the substrate topography but not by substrate rigidity. SaI/N morphology and migration seem to escape from extracellular cues: the cells exhibit uncorrelated migration trajectories and a large dispersion of their migration speed, which increases with substrate rigidity.
细胞黏附和迁移受到细胞外基质(ECM)结构和硬度的强烈影响,但对于此类环境信号对细胞反应的协同影响知之甚少,尤其是当考虑来源和形态相似但表现出正常或癌性表型的细胞时。使用具有可调硬度(500 kPa、750 kPa、2000 kPa)和形貌(线条、柱体或无图案)的微图案化聚二甲基硅氧烷底物(PDMS),我们系统地分析了正常(3T3)和成纤维癌细胞(SaI/N)的差异反应。我们的结果表明,两种细胞对底物硬度和微观形貌的变化均表现出不同的形态和运动反应。3T3细胞的极化和铺展受底物微观形貌和硬度的影响。细胞表现出持续的迁移类型,这取决于底物各向异性。相比之下,SaI/N细胞铺展的动力学受到底物形貌的强烈影响,但不受底物硬度的影响。SaI/N细胞的形态和迁移似乎不受细胞外信号的影响:细胞表现出不相关的迁移轨迹,其迁移速度分散性很大,且随着底物硬度的增加而增大。