Breckenridge Mark T, Desai Ravi A, Yang Michael T, Fu Jianping, Chen Christopher S
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Cell Mol Bioeng. 2014 Mar;7(1):26-34. doi: 10.1007/s12195-013-0307-6. Epub 2013 Oct 9.
Rigidity sensing plays a fundamental role in multiple cell functions ranging from migration, to proliferation and differentiation. During migration, single cells have been reported to preferentially move toward more rigid regions of a substrate in a process termed . could contribute to cell migration in wound healing and gastrulation, where local gradients in tissue rigidity have been described. Despite the potential importance of this phenomenon to physiology and disease, it remains unclear how rigidity guides these behaviors and the underlying cellular and molecular mechanisms. To investigate the functional role of subcellular distribution and dynamics of cellular traction forces during durotaxis, we developed a unique microfabrication strategy to generate elastomeric micropost arrays patterned with regions exhibiting two different rigidities juxtaposed next to each other. After initial cell attachment on the rigidity boundary of the micropost array, NIH 3T3 fibroblasts were observed to preferentially migrate toward the rigid region of the micropost array, indicative of durotaxis. Additionally, cells bridging two rigidities across the rigidity boundary on the micropost array developed stronger traction forces on the more rigid side of the substrate indistinguishable from forces generated by cells exclusively seeded on rigid regions of the micropost array. Together, our results highlighted the utility of step-rigidity micropost arrays to investigate the functional role of traction forces in rigidity sensing and , suggesting that cells could sense substrate rigidity locally to induce an asymmetrical intracellular traction force distribution to contribute to .
硬度感知在从迁移到增殖和分化的多种细胞功能中发挥着基本作用。在迁移过程中，据报道单个细胞在一个称为 的过程中优先向底物更硬的区域移动。这可能有助于伤口愈合和原肠胚形成过程中的细胞迁移，其中已经描述了组织硬度的局部梯度。尽管这种现象对生理学和疾病具有潜在重要性，但尚不清楚硬度如何引导这些行为以及潜在的细胞和分子机制。为了研究细胞牵引力的亚细胞分布和动力学在趋硬性过程中的功能作用，我们开发了一种独特的微制造策略，以生成弹性微柱阵列，该阵列图案化有彼此相邻并置且具有两种不同硬度的区域。在微柱阵列的硬度边界上最初的细胞附着后，观察到NIH 3T3成纤维细胞优先向微柱阵列的硬区域迁移，这表明存在趋硬性。此外，在微柱阵列上跨越硬度边界连接两种硬度的细胞在底物较硬的一侧产生了更强的牵引力，这与仅接种在微柱阵列硬区域的细胞产生的力没有区别。总之，我们的结果突出了阶梯硬度微柱阵列在研究牵引力在硬度感知中的功能作用方面的效用，表明细胞可以局部感知底物硬度以诱导不对称的细胞内牵引力分布，从而有助于 。
