不同弹性的细胞外基质（Extracellular Matrix，ECM）可以诱导间充质干细胞分化为成神经细胞、成肌肉细胞、成骨细胞等，这一神奇的现象自2006年一经发表，就引起全球众多科学家的关注。5年来，国际生物力学界数年来一直不断探索其机理。*近这个迷人的问题有望得到解答。
细胞感受ECM弹性的过程是细胞将感受到的力学刺激转化为生物化学信号的过程。该过程称为细胞力学信号转导。细胞通过黏着斑与ECM黏附。黏着斑由一系列信号分子构成，并在胞质中与细胞微丝骨架相连。这些信号分子在力学刺激作用下可产生构象变化，从而触发激酶活化、磷酸化位点暴露、信号分子胞内运输和受体配体结合强度改变等一系列分子事件。在这些信号分子中，整合素在已知的多数力学信号感知过程中都起到关键作用，是力学信号转导通路的重要起点。
研究人员在论文中阐述了细胞外基质弹性诱导干细胞世系分化的研究的重要进展：较软的细胞外基质（ExtracellularMatrix，ECM）易使整合素-基质蛋白复合物解离，从而触发整合素分子被细胞内吞，导致骨形态蛋白受体的亚细胞定位发生改变，使其下游信号通路被抑制，*终诱导干细胞向神经系分化。力学分析表明：材料的弹性变化影响了整合素-基质蛋白复合物上的加载速率，因此影响了该复合物的解离力。
清华大学航天航空学院生物力学所的教师杨春与加州大学圣地亚哥分校的钱煦教授为这篇论文的共同通讯作者。该项研究由自然科学基金和科技部“973”项目等资助。
推荐原文索引：
Integrin activation and internalization on soft ECM as amechanism of induction of stem cell differentiation by ECMelasticity
The mechanism by which ECM elasticity induces lineagespecification of stem cells has not been clearly understood.Integrins are well-documented mechanosensors that are positioned atthe beginning of the sensing pathway. By using an antibodyspecifically recognizing the active conformation of β1 integrin, weobserved that β1 integrin activation in bone marrow mesenchymalstem cells (BMMSCs) was induced by soft substrate to asignificantly greater degree than by stiff substrate. In contrast,however, the level of cell surface integrin on soft substrate wassignificantly lower than that on stiff substrate. Soft substratemarkedly enhanced the internalization of integrin, and thisinternalization was mediated mainly through caveolae/raft-dependentendocytosis. The inhibition of integrin internalization blocked theneural lineage specification of BMMSCs on soft substrate.Furthermore, soft substrate also repressed the bone morphogeneticprotein (BMP)/Smad pathway at least partially throughintegrin-regulated BMP receptor endocytosis. A theoretical analysisbased on atomic force microscopy (AFM) data indicated thatintegrin–ligand complexes are more easily ruptured on softsubstrate; this outcome may contribute to the enhancement ofintegrin internalization on soft substrate. Taken together, ourresults suggest that ECM elasticity affects integrin activity andtrafficking to modulate integrin BMP receptor internalization, thuscontributing to stem cell lineage specification.