School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Department of Aerospace Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
J R Soc Interface. 2017 Oct;14(135). doi: 10.1098/rsif.2017.0287.
Fibroblast migration plays a key role during various physiological and pathological processes. Although migration of individual fibroblasts has been well studied, migration often involves simultaneous locomotion of fibroblasts sited in close proximity, so-called ' migration', during which intensive cell-cell interactions occur. This study aims to understand the effects of matrix mechanical environments on the cell-matrix and cell-cell interactions during migration of fibroblasts on collagen matrices. Specifically, we hypothesized that a group of migrating cells can significantly deform the matrix, whose mechanical microenvironment dramatically changes compared with the undeformed state, and the alteration of the matrix microenvironment reciprocally affects cell migration. This hypothesis was tested by time-resolved measurements of cell and extracellular matrix movement during migration on collagen hydrogels with varying concentrations. The results illustrated that a group of cells generates significant spatio-temporal deformation of the matrix before and during the migration. Cells on soft collagen hydrogels migrate along tortuous paths, but, as the matrix stiffness increases, cell migration patterns become aligned with each other and show coordinated migration paths. As cells migrate, the matrix is locally compressed, resulting in a locally stiffened and dense matrix across the collagen concentration range studied.
成纤维细胞迁移在各种生理和病理过程中起着关键作用。尽管单个成纤维细胞的迁移已经得到了很好的研究，但迁移通常涉及到紧密相邻的成纤维细胞的同时运动，即所谓的“群集迁移”，在此过程中会发生密集的细胞间相互作用。本研究旨在了解基质力学环境对成纤维细胞在胶原基质上迁移过程中细胞-基质和细胞-细胞相互作用的影响。具体而言，我们假设一组迁移的细胞可以显著地改变基质的形状，其力学微环境与未变形状态相比会发生显著变化，而基质微环境的改变又会反过来影响细胞迁移。通过在不同浓度的胶原水凝胶上迁移过程中对细胞和细胞外基质运动进行时间分辨测量，验证了这一假说。结果表明，在迁移之前和期间，一组细胞会对基质产生显著的时空变形。在软胶原水凝胶上，细胞沿曲折的路径迁移，但随着基质硬度的增加，细胞迁移模式彼此对齐，并表现出协调的迁移路径。随着细胞的迁移，基质会被局部压缩，导致在研究的胶原浓度范围内的局部基质变硬和变密。
