Elucidating the Role of Matrix Stiffness in 3D Cell Migration and Remodeling
Elucidating the Role of Matrix Stiffness in 3D Cell Migration and Remodeling
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DOI：
10.1016/j.bpj.2010.11.082
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发表时间：
2011-01-19
影响因子：
3.4
通讯作者：
Lutolf, M. P.
中科院分区：
文献类型：
--
作者：
Ehrbar, M.;Sala, A.;Lutolf, M. P.
以高度受控的方式模拟特定细胞外基质功能的还原论者体外模型系统（称为人工细胞外基质（aECM））已越来越多地用于阐明细胞-ECM相互作用在调节细胞命运中的作用。为了更好地理解生物物理和生物化学效应物在控制三维细胞迁移中的相互作用，在本研究中使用基于聚（乙二醇）的aECM平台来探索基质交联密度（此处由刚度表示）对体外和体内细胞迁移的影响。在体外，迁移行为的单一前成骨细胞内的水凝胶不同的刚度和易降解的基质金属蛋白酶的时间推移显微镜进行了评估。迁移行为被认为是强烈依赖于基质刚度，确定了两个制度：一个nonproteolytic迁移模式占主导地位，在相对较低的基质刚度和蛋白水解迁移在较高的刚度。随后的体内实验显示了类似的刚度依赖性的基质重塑，虽然不太敏感的基质金属蛋白酶的敏感性。因此，我们的aECM模型系统非常适合于揭示生理相关细胞迁移现象的生物物理和生物化学决定因素的作用。
Reductionist in vitro model systems which mimic specific extracellular matrix functions in a highly controlled manner, termed artificial extracellular matrices (aECM), have increasingly been used to elucidate the role of cell-ECM interactions in regulating cell fate. To better understand the interplay of biophysical and biochemical effectors in controlling three-dimensional cell migration, a poly(ethylene glycol)-based aECM platform was used in this study to explore the influence of matrix cross-linking density, represented here by stiffness, on cell migration in vitro and in vivo. In vitro, the migration behavior of single preosteoblastic cells within hydrogels of varying stiffness and susceptibilities to degradation by matrix metalloproteases was assessed by time-lapse microscopy. Migration behavior was seen to be strongly dependent on matrix stiffness, with two regimes identified: a nonproteolytic migration mode dominating at relatively low matrix stiffness and proteolytic migration at higher stiffness. Subsequent in vivo experiments revealed a similar stiffness dependence of matrix remodeling, albeit less sensitive to the matrix metalloprotease sensitivity. Therefore, our aECM model system is well suited to unveil the role of biophysical and biochemical determinants of physiologically relevant cell migration phenomena.