Defining the role of syndecan-4 in mechanotransduction using surface-modification approaches
Defining the role of syndecan-4 in mechanotransduction using surface-modification approaches
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DOI：
10.1073/pnas.0902639106
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发表时间：
2009-12-29
影响因子：
11.1
通讯作者：
LeDuc, Philip R.
中科院分区：
文献类型：
--
作者：
Bellin, Robert M.;Kubicek, James D.;LeDuc, Philip R.
细胞对外界机械刺激的反应能力是一个复杂而强大的过程，涉及多种分子相互作用。尽管已经对机械转导进行了大量的研究，但关于物理刺激和生化反应之间的联系仍然存在许多问题。值得注意的是所涉及的跨膜蛋白的贡献，特别是整合素，因为它们与细胞外基质和细胞骨架都有联系。在这里，我们证明了一种基于机械的引发分子Syndecan-4的存在。我们首先展示了Syndecan-4分子在没有整合素直接细胞外结合的情况下支持细胞附着和扩散的能力。我们还通过控制具有与活细胞结合的分子特异性的珠子的表面相互作用来检查焦点黏附相关蛋白的分布。此外，在通过Syndecan-4特定的附着物将细胞附着到弹性体膜上后，我们通过我们的机械刺激和聚合物表面化学修饰的方法来机械地拉紧细胞。通过我们的基于弹性体膜的方法和Syndecan-4的光磁扭曲细胞术，我们发现ERK的磷酸化类似于对基于整合素的细胞附着的机械转导反应。最后，通过使用细胞骨架干扰剂，这种机械信号被证明是肌动蛋白细胞骨架依赖的。我们相信，这些结果将对包括机械转导、Syndecan生物学和细胞-材料相互作用在内的广泛领域产生兴趣。
The ability of cells to respond to external mechanical stimulation is a complex and robust process involving a diversity of molecular interactions. Although mechanotransduction has been heavily studied, many questions remain regarding the link between physical stimulation and biochemical response. Of significant interest has been the contribution of the transmembrane proteins involved, and integrins in particular, because of their connectivity to both the extracellular matrix and the cytoskeleton. Here, we demonstrate the existence of a mechanically based initiation molecule, syndecan-4. We first demonstrate the ability of syndecan-4 molecules to support cell attachment and spreading without the direct extracellular binding of integrins. We also examine the distribution of focal adhesion-associated proteins through controlling surface interactions of beads with molecular specificity in binding to living cells. Furthermore, after adhering cells to elastomeric membranes via syndecan-4-specific attachments we mechanically strained the cells via our mechanical stimulation and polymer surface chemical modification approach. We found ERK phosphorylation similar to that shown for mechanotransductive response for integrin-based cell attachments through our elastomeric membrane-based approach and optical magnetic twisting cytometry for syndecan-4. Finally, through the use of cytoskeletal disruption agents, this mechanical signaling was shown to be actin cytoskeleton dependent. We believe that these results will be of interest to a wide range of fields, including mechanotransduction, syndecan biology, and cell-material interactions.