Specific Cell Adhesion at Nano-Biointerfaces: Synergistic Effect of Topographical Matching and Molecular Recognition.

Specific cell adhesion is essential for functional biointerfaces, especially in cancer diagnosis. However, the role of surface nanotopography in this process remains unclear. Herein, we reveal the critical role of surface nanotopography by measuring adhesion forces utilizing fluidic force microscopy (FluidFM). The antibody-coated nanospiky surface exhibits cell adhesion force 1 to 2 orders of magnitude higher than those of the flat, nanospiky, and antibody-coated flat surfaces. This amplified effect is related to a time-dependent reversal, with adhesion force on nanospiky surfaces initially weaker than that on flat surfaces but eventually surpassing it. Mathematical simulations further demonstrate that micro-nanostructured surfaces maximize contact points, enabling multiscale, multipoint cell-substrate interactions, consistent with experimental results. From thermodynamic and kinetic perspectives, we propose a multiscale, multipoint recognition model based on the synergistic effect of topographical matching and molecular recognition. Our findings provide valuable clues for biointerface design in cancer diagnosis, drug screening, and tissue engineering.