Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
ACS Appl Mater Interfaces. 2010 Aug;2(8):2317-24. doi: 10.1021/am100346k.
Cell migration plays a critical role in numerous physiological processes, such as wound healing, response to inflammation, and cancer metastasis. In recent years, accumulating evidence indicates that cell movement is regulated not only by chemical signals but also by mechanical stimuli. In this study, the primary goal is to identify whether a chemical or mechanical stimulus plays the decisive role in directing cell migration. Measuring the motility of cells when they are presented with a combination of chemical and mechanical cues will provide insight into the complex physiological phenomena that guide and direct migration. A novel polyacrylamide hydrogel was designed with an interfacial region where the chemical and mechanical properties varied in opposing directions. One side of the interface was stiff (high Young's modulus) with a low protein concentration, whereas the other side of the interface was compliant (low Young's modulus) with a high protein concentration. The chemical gradient was created by varying the collagen (type I) concentration and the mechanical gradient was introduced by changing the extent of cross-linking in the polymer. The length of the interface with opposing chemical-mechanical profiles was found to be approximately 100 mum. Our results demonstrate that when Balb/c 3T3 fibroblasts were presented with a choice, they either migrated preferentially toward the high-collagen-compliant (low Young's modulus) side of the interfacial region or remained on the high-collagen region, suggesting a more dominant role for chemical stimuli in directing fibroblast locomotion.
细胞迁移在许多生理过程中起着至关重要的作用，如伤口愈合、炎症反应和癌症转移。近年来，越来越多的证据表明，细胞的运动不仅受到化学信号的调节，还受到机械刺激的调节。在这项研究中，主要目标是确定是化学刺激还是机械刺激在指导细胞迁移中起决定性作用。测量细胞在受到化学和机械刺激的组合时的迁移能力，将深入了解指导和引导迁移的复杂生理现象。设计了一种具有界面区域的新型聚丙烯酰胺水凝胶，该区域的化学和机械性质呈相反方向变化。界面的一侧是刚性的（杨氏模量高），蛋白浓度低，而界面的另一侧是顺应性的（杨氏模量低），蛋白浓度高。通过改变胶原（I 型）浓度来产生化学梯度，通过改变聚合物的交联程度来引入机械梯度。发现具有相反化学-机械特性的界面长度约为 100 微米。我们的结果表明，当 Balb/c 3T3 成纤维细胞面临选择时，它们要么优先迁移到高胶原顺应性（低杨氏模量）的界面区域一侧，要么停留在高胶原区域，这表明化学刺激在指导成纤维细胞运动中起着更主导的作用。
