Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610065, China.
Department of Electrical and Electronic Engineering, The University of Hong Kong, Pok Fu Lam, Hong Kong 999077, China.
Nano Lett. 2024 Jul 3;24(26):7953-7961. doi: 10.1021/acs.nanolett.4c01371. Epub 2024 Jun 18.
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.
纳米级细胞-细胞外基质 (ECM) 配体的物理特性对生物学过程（如黏附、迁移和分化）有深远影响。虽然细胞对静态配体的力学响应已有深入研究，但具有“自适应”特性的动态配体呈现对细胞力学转导的影响仍知之甚少。我们利用可控的可扩散配体界面证明，表面配体快速扩散时，细胞可通过激活整合素α5β1 募集配体，从而在早期黏附阶段更快地形成和扩展焦点黏附。利用紫外线敏感的锚定分子触发配体的“动态到静态”转变，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通过操纵分子动力学直接影响干细胞命运，提示了“顺序”控制的可移动表面作为智能生物材料涂层工程适应性平台的潜力。
