Dynamic Regulation of Cell Mechanotransduction through Sequentially Controlled Mobile Surfaces.

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 α5ß1, 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 α5ß1 and αvß3 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.

Hierarchical Fluid Interface Enables Spatiotemporal Regulation of Ligand Distribution to Increase Kinetics and Thermodynamics of Interfacial Binding Reaction.

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.