Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels
Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels
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DOI：
10.1038/nmat4483
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发表时间：
2016-03-01
期刊：
影响因子：
41.2
通讯作者：
Rowan, Alan E.
中科院分区：
文献类型：
--
作者：
Das, Rajat K.;Gocheva, Veronika;Rowan, Alan E.
整体基质刚度已成为干细胞分化的关键机械线索。在这里，我们展示了包裹在生理软（类似于0.2-0.4 kPa）的人间充质干细胞的承诺和分化，完全合成的基于多异氰酸肽的三维（3D）基质，模拟成体干细胞龛的刚度并显示生物聚合物样的应力硬化，可以很容易地通过改变应力硬化的开始而从脂肪形成转变为成骨形成。这种机械行为可以通过简单地改变材料的聚合物长度来调节，同时保持刚度和配体密度。我们的研究结果将应力硬化作为3D微环境中控制干细胞命运的重要参数，并揭示了硬化发生与微管相关蛋白DCAMKL1表达之间的相关性，从而暗示DCAMKL1参与应力硬化介导的机械转导途径，该途径涉及干细胞成骨过程中的微管动力学。
Bulk matrix stiffness has emerged as a key mechanical cue in stem cell differentiation. Here, we show that the commitment and differentiation of human mesenchymal stem cells encapsulated in physiologically soft (similar to 0.2-0.4 kPa), fully synthetic polyisocyanopeptide-based three-dimensional (3D) matrices that mimic the stiffness of adult stem cell niches and show biopolymer-like stress stiffening, can be readily switched from adipogenesis to osteogenesis by changing only the onset of stress stiffening. This mechanical behaviour can be tuned by simply altering the material's polymer length whilst maintaining stiffness and ligand density. Our findings introduce stress stiffening as an important parameter that governs stem cell fate in a 3D microenvironment, and reveal a correlation between the onset of stiffening and the expression of the microtubule-associated protein DCAMKL1, thus implicating DCAMKL1 in a stress-stiffening-mediated, mechanotransduction pathway that involves microtubule dynamics in stem cell osteogenesis.