Nanotopography as modulator of human mesenchymal stem cell function.
Nanotopography as modulator of human mesenchymal stem cell function.
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DOI：
10.1016/j.biomaterials.2012.03.053
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发表时间：
2012-07
期刊：
影响因子：
14
通讯作者：
Leong, Kam W.
中科院分区：
文献类型：
--
作者：
Kulangara, Karina;Yang, Yong;Yang, Jennifer;Leong, Kam W.
纳米形貌改变了人间充质干细胞（hMSC）从形状到分化潜能的变化；然而，人们对其潜在的分子机制知之甚少。本文研究了hMSC在350 nm光栅形貌的聚二甲基硅氧烷基质上的培养，并利用生化和成像技术研究了焦点粘附组成和动力学。我们的研究结果表明，酶蛋白在hMSC对纳米形貌的反应中起着关键作用。在350 nm光栅上，Zyxin表达下调，导致更小、更动态的焦点粘附。由于zyxin与黏附的关联是力依赖的，较小的zyxin阳性黏附及其较高的周转率表明350nm形貌上黏附的牵引力降低。这些变化导致在350nm光栅上更快和更有方向性的迁移。这些研究结果表明，纳米形貌降低了hMSC中作用于焦点粘附的机械力，并表明350 nm光栅形貌下，酶合蛋白表达和动力学的力依赖变化是焦点粘附重塑的基础，从而导致hMSC功能的调节。
Nanotopography changes human mesenchymal stem cells (hMSC) from their shape to their differentiation potential; however little is known about the underlying molecular mechanisms. Here we study the culture of hMSC on polydimethylsiloxane substrates with 350 nm grating topography and investigate the focal adhesion composition and dynamics using biochemical and imaging techniques. Our results show that zyxin protein plays a key role in the hMSC response to nanotopography. Zyxin expression is downregulated on 350 nm gratings, leading to smaller and more dynamic focal adhesion. Since the association of zyxin with focal adhesions is force-dependent, smaller zyxin-positive adhesion as well as its higher turnover rate suggests that the traction force in focal adhesion on 350 nm topography is decreased. These changes lead to faster and more directional migration on 350 nm gratings. These findings demonstrate that nanotopography decreases the mechanical forces acting on focal adhesions in hMSC and suggest that force-dependent changes in zyxin protein expression and kinetics underlie the focal adhesion remodeling in response to 350 nm grating topography, resulting in modulation of hMSC function.
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DOI：
10.1073/pnas.0903269107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Kilian, Kristopher A.;Bugarija, Branimir;Mrksich, Milan
通讯作者：
Mrksich, Milan
影响因子：
3.4
作者：
Kulangara, Karina;Leong, Kam W.
通讯作者：
Leong, Kam W.
影响因子：
5.6
作者：
Lele, TP;Pendse, J;Ingber, DE
通讯作者：
Ingber, DE
DOI：
10.1083/jcb.200204153
发表时间：
2002-11-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Galbraith CG;Yamada KM;Sheetz MP
通讯作者：
Sheetz MP
影响因子：
5.6
作者：
Peyton, SR;Putnam, AJ
通讯作者：
Putnam, AJ