Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and mechanical properties of human mesenchymal stem cells.
Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and mechanical properties of human mesenchymal stem cells.
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DOI：
10.1016/j.biomaterials.2009.10.037
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发表时间：
2010-02
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：
Yim, Evelyn K. F.;Darling, Eric M.;Kulangara, Karina;Guilak, Farshid;Leong, Kam W.
关键词：
干细胞的生长可以通过物理因素如细胞外基质纳米形貌来调节。我们假设纳米形貌通过改变整合素聚集和粘着斑（FA）组装来调节细胞行为，从而导致细胞骨架组织和细胞力学性质的变化。在350 nm光栅的组织培养聚苯乙烯（TCPS）和聚二甲基硅氧烷（PDMS）上培养的人骨髓间充质干细胞（hMSCs）显示整合素亚基α2、α6、αV、β2、β3和β4的表达与未图案化的对照相比降低。在光栅上，伸长的hMSCs表现出对齐的肌动蛋白细胞骨架，而在未图案化的对照组中，伸展的细胞表现出随机但更密集的肌动蛋白细胞骨架网络。细胞骨架和FA组件的表达也被改变的纳米形貌所反映的原子力显微镜（AFM）压痕测量的机械性能。在刚性TCPS上，光栅上的hMSCs表现出较低的瞬时和平衡杨氏模量和表观粘度。在较软的PDMS上，纳米形貌的影响不显著。然而，在PDMS上培养的hMSCs显示出比在TCPS上培养的hMSCs更低的细胞力学性能，无论地形如何。这表明，纳米形貌和基板刚度可能是重要的，在确定机械性能，而纳米形貌可能是更占主导地位的细胞骨架和脂肪酸的组织。
The growth of stem cells can be modulated by physical factors such as extracellular matrix nanotopography. We hypothesize that nanotopography modulates cell behavior by changing the integrin clustering and focal adhesion (FA) assembly, leading to changes in cytoskeletal organization and cell mechanical properties. Human mesenchymal stem cells (hMSCs) cultured on 350nm gratings of tissue-culture polystyrene (TCPS) and polydimethylsiloxane (PDMS) showed decreased expression of integrin subunits α2, α6, αV, β2, β3 and β4 compared to the unpatterned controls. On gratings, the elongated hMSCs exhibited an aligned actin cytoskeleton, while on unpatterned controls, spreading cells showed a random but denser actin cytoskeleton network. Expression of cytoskeleton and FA components was also altered by the nanotopography as reflected in the mechanical properties measured by atomic force microscopy (AFM) indentation. On the rigid TCPS, hMSCs on gratings exhibited lower instantaneous and equilibrium Young’s moduli and apparent viscosity. On the softer PDMS, the effects of nanotopography were not significant. However, hMSCs cultured on PDMS showed lower cell mechanical properties than those on TCPS, regardless of topography. These suggest that both nanotopography and substrate stiffness could be important in determining mechanical properties, while nanotopography may be more dominant in determining the organization of the cytoskeleton and FAs.
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