关键词: biointerfaces cell adhesion diffusible ligands ligand recruitment mechanotransduction

Mesh : Mechanotransduction, Cellular Mesenchymal Stem Cells / cytology Cell Differentiation Cell Adhesion Humans Surface Properties Integrin alpha5beta1 / metabolism Osteogenesis Extracellular Matrix / chemistry metabolism Integrin alphaVbeta3 / metabolism Ligands Focal Adhesions

来  源:   DOI:10.1021/acs.nanolett.4c01371

Abstract:
The physical properties of nanoscale cell-extracellular matrix (ECM) ligands profoundly impact biological processes, such as adhesion, motility, and differentiation. While the mechanoresponse of cells to static ligands is well-studied, the effect of dynamic ligand presentation with \"adaptive\" properties on cell mechanotransduction remains less understood. Utilizing a controllable diffusible ligand interface, we demonstrated that cells on surfaces with rapid ligand mobility could recruit ligands through activating integrin α5β1, leading to faster focal adhesion growth and spreading at the early adhesion stage. By leveraging UV-light-sensitive anchor molecules to trigger a \"dynamic to static\" transformation of ligands, we sequentially activated α5β1 and αvβ3 integrins, significantly promoting osteogenic differentiation of mesenchymal stem cells. This study illustrates how manipulating molecular dynamics can directly influence stem cell fate, suggesting the potential of \"sequentially\" controlled mobile surfaces as adaptable platforms for engineering smart biomaterial coatings.
摘要:
纳米级细胞-细胞外基质(ECM)配体的物理性质深刻影响生物过程,如附着力,运动性,和差异化。虽然细胞对静态配体的机械反应已得到充分研究,具有“适应性”特性的动态配体呈递对细胞机械转导的影响尚不清楚。利用可控的可扩散配体界面,我们证明,具有快速配体迁移的表面上的细胞可以通过激活整合素α5β1来募集配体,从而在早期粘附阶段导致更快的局灶性粘附生长和扩散。通过利用紫外光敏感的锚分子来触发配体的“动态到静态”转化,我们依次激活α5β1和αvβ3整合素,显著促进间充质干细胞的成骨分化。这项研究说明了如何操纵分子动力学可以直接影响干细胞的命运,这表明“顺序”控制的移动表面作为工程智能生物材料涂层的适应性平台的潜力。
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