Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.
Histide, Chaltenbodenstrasse 8, 8834 Schindellegi, Switzerland.
Nat Mater. 2016 Mar;15(3):318-25. doi: 10.1038/nmat4483. Epub 2015 Nov 30.
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 (∼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.
基质硬度已成为干细胞分化的关键力学线索。在这里，我们表明，在生理上柔软（约 0.2-0.4 kPa）的完全合成的聚异氰酸酯肽基三维（3D）基质中包封的人间充质干细胞的分化和分化，可以通过仅改变起始应力变硬来轻松地从脂肪生成切换到成骨生成。通过简单地改变材料的聚合物长度，同时保持刚度和配体密度，可以调整这种机械行为。我们的发现将应力变硬引入到 3D 微环境中控制干细胞命运的重要参数，并揭示了变硬起始与微管相关蛋白 DCAMKL1 表达之间的相关性，从而表明 DCAMKL1 参与涉及微管动力学的应力变硬介导的机械转导途径在干细胞成骨过程中。
