Department of Materials Science and Engineering, SUNY at Stony Brook, Stony Brook, New York, USA.
Department of Biomedical Engineering, SUNY at Stony Brook, Stony Brook, New York, USA.
J Invest Dermatol. 2013 Oct;133(10):2471-2479. doi: 10.1038/jid.2013.184. Epub 2013 Apr 17.
En masse cell migration is more relevant compared with single-cell migration in physiological processes of tissue formation, such as embryogenesis, morphogenesis, and wound healing. In these situations, cells are influenced by the proximity of other cells including interactions facilitated by substrate mechanics. Here, we found that when fibroblasts migrated en masse over a hydrogel, they established a well-defined deformation field by traction forces and migrated along a trajectory defined by field gradients. The mechanics of the hydrogel determined the magnitude of the gradient. For materials stiff enough to withstand deformation related to cellular traction forces, such patterns did not form. Furthermore, migration patterns functioned poorly on very soft matrices where only a minimal traction gradient could be established. The largest degree of alignment and migration velocity occurred on the gels with the largest gradients. Granulation tissue formation in punch wounds of juvenile pigs was correlated strongly with the modulus of the implanted gel, in agreement with in vitro en masse cell migration studies. These findings provide basic insight into the biomechanical influences on fibroblast movement in early wounds and relevant design criteria for the development of tissue-engineered constructs that aim to stimulate en masse cell recruitment for rapid wound healing.
与单细胞迁移相比，群体细胞迁移在组织形成的生理过程中更为重要，如胚胎发生、形态发生和伤口愈合。在这些情况下，细胞会受到其他细胞的邻近影响，包括由基质力学促进的相互作用。在这里，我们发现当成纤维细胞在水凝胶上大规模迁移时，它们通过牵引力建立了一个明确的变形场，并沿着由场梯度定义的轨迹迁移。水凝胶的力学决定了梯度的大小。对于足以承受与细胞牵引力相关的变形的材料，这种模式不会形成。此外，在非常柔软的基质上，只能建立最小的牵引力梯度，迁移模式的功能很差。在梯度最大的凝胶上，排列和迁移速度达到最大程度。幼年猪的穿孔伤口中的肉芽组织形成与植入凝胶的模量强烈相关，与体外大规模细胞迁移研究一致。这些发现为早期伤口中成纤维细胞运动的生物力学影响提供了基本的见解，并为开发旨在刺激大规模细胞募集以实现快速伤口愈合的组织工程构建体提供了相关的设计标准。
