ligand recruitment

  • 文章类型: Journal Article
    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。
    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.
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  • 文章类型: Journal Article
    在大自然中,界面内的受体-配体结合反应通常通过调节界面受体/配体的时空分布来获得最佳的结合动力学和热力学。受此启发,我们报告了一种分层流体界面(HieFluidFace)来调节界面配体的时空分布,以增加界面结合反应的速率和热力学有利性。每个球形适体(SAPT)锚定在支撑的脂质双层上,没有流动性,作为“岛”,并被许多具有自由流动性的荧光适体(FAPT)包围,如“木筏”。这种配体“岛筏”模型为快速结合提供了大的反应性横截面。SAPT和FAPT的协同多价改善了紧密捕获的界面亲和力。此外,FAPT在结合位点处积累以结合细胞受体,并具有成簇的荧光以“减轻”细胞以进行直接鉴定。因此,微流控芯片中的HieFluidFace实现了从临床样品中高效捕获和识别循环肿瘤细胞,提供了一个新的范式来优化界面结合反应的动力学和热力学。
    In nature, regulation of the spatiotemporal distribution of interfacial receptors and ligands leads to optimum binding kinetics and thermodynamics of receptor-ligand binding reactions within interfaces. Inspired by this, we report a hierarchical fluid interface (HieFluidFace) to regulate the spatiotemporal distribution of interfacial ligands to increase the rate and thermodynamic favorability of interfacial binding reactions. Each aptamer-functionalized gold nanoparticle, termed spherical aptamer (SAPT), is anchored on a supported lipid bilayer without fluidity, like an \"island\", and is surrounded by many fluorescent aptamers (FAPTs) with free fluidity, like \"rafts\". Such ligand \"island-rafts\" model provides a large reactive cross-section for rapid binding to cellular receptors. The synergistic multivalency of SAPTs and FAPTs improves interfacial affinity for tight capture. Moreover, FAPTs accumulate at binding sites to bind to cellular receptors with clustered fluorescence to \"lighten\" cells for direct identification. Thus, HieFluidFace in a microfluidic chip achieves high-performance capture and identification of circulating tumor cells from clinical samples, providing a new paradigm to optimize the kinetics and thermodynamics of interfacial binding reactions.
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