Surface Atomic Structure Directs the Fate of Human Mesenchymal Stem Cells
Surface Atomic Structure Directs the Fate of Human Mesenchymal Stem Cells
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表面原子结构指导人类间充质干细胞的命运
DOI：
10.1021/acsami.7b02411
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发表时间：
2017-05-10
影响因子：
9.5
通讯作者：
Wang, Huiming
中科院分区：
文献类型：
--
作者：
Dong, Lingqing;Chen, Kui;Wang, Huiming
与材料接触的干细胞能够感知其表面特征，通过信号转导途径整合细胞外基质（ECM）蛋白线索，并最终指导细胞命运决定。然而，由于ECM环境中存在复杂的多组分信号环境，发现干细胞如何响应固有材料表面特征的跨学科机制仍然是一个挑战。在这里，我们证明了人类间充质干细胞（hMSCs）的命运可以由材料表面的固有物理线索调节到原子尺度特征。TiO-封端的SrTiO 3 {110}基底上的hMSC倾向于分化成特定谱系细胞（成骨细胞、软骨细胞、脂肪细胞），而TiO 2-封端的SrTiO 3 {100}基底上的hMSC倾向于维持多能性。实验观察和分子动力学模拟表明，最初吸附的血清白蛋白和纤连蛋白蛋白的不同构象激活整合素粘着斑细胞骨架肌动蛋白转导途径，随后，指导hMSCs的基因和蛋白质表达。此外，我们证明了初始蛋白质吸附行为是依赖于不同的羟基基团源自不同的表面原子结构以及功函数。因此，这项工作为细胞材料相互作用的基本理解提供了新的见解，并将对进一步设计材料以指导干细胞命运产生深远的影响。
Stem cells in contact with materials are able to sense their surface features, integrate extracellular matrix (ECM) protein cues through a signal transduction pathway, and ultimately direct cell fate decisions. However, discovering the interdisciplinary mechanisms of how stem cells respond to inherent material surface features still remains a challenge due to the complex, multicomponent signaling milieu present in the ECM environment. Here, we demonstrate that the fate of human mesenchymal stem cells (hMSCs) can be regulated by the inherent physical cue of the material surface down to atomic-scale features. hMSCs on a TiO-terminated SrTiO3 {110} substrate tend to differentiate into specific lineage cells (osteoblast, chondrocyte, adipocyte), whereas on a TiO2-terminated SrTiO3 {100} substrate they are prone to maintain pluripotency. The experimental observations and molecular dynamics simulations indicate that the distinct conformations of the initially adsorbed serum albumin and fibronectin proteins activate the integrin focal adhesion cytoskeleton actin transduction pathway and, subsequently, direct the gene and protein expressions of hMSCs. Moreover, we demonstrate that the initial protein adsorption behaviors are dependent on the distinct hydroxyl groups originating from different surface atomic structures as well as the work functions. This work, therefore, provides new insights into the fundamental understanding of cell material interactions and will have a profound impact on-further designing materials to direct the stem cell fate.