Hydrogels with tunable stress relaxation regulate stem cell fate and activity.
Hydrogels with tunable stress relaxation regulate stem cell fate and activity.
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DOI：
10.1038/nmat4489
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发表时间：
2016-03
期刊：
影响因子：
41.2
通讯作者：
Mooney DJ
中科院分区：
文献类型：
--
作者：
Chaudhuri O;Gu L;Klumpers D;Darnell M;Bencherif SA;Weaver JC;Huebsch N;Lee HP;Lippens E;Duda GN;Mooney DJ
天然细胞外基质（ECM）是粘弹性的，并表现出应力松弛。然而，用作用于三维（3D）培养的合成ECM的水凝胶通常是弹性的。在这里，我们报告了一种材料的方法来调整3D培养水凝胶的应力松弛速率，独立于水凝胶的初始弹性模量，细胞粘附配体密度和降解。我们发现，细胞的扩展，增殖和间充质干细胞（MSCs）的成骨分化都增强了细胞培养在凝胶中具有更快的松弛。引人注目的是，MSC在快速松弛的水凝胶中形成矿化的富含胶原蛋白-1的基质，其初始弹性模量为17 kPa。我们还表明，应力松弛的影响介导的粘附配体结合，肌动球蛋白收缩和机械集群的粘附配体。我们的研究结果强调了应力松弛作为细胞-ECM相互作用的关键特征和作为用于细胞培养的生物材料的重要设计参数。
Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel’s initial elastic modulus, cell-adhesion-ligand density and degradation. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture.