Biomimetic Molecular Tweezing at Biointerfaces: A Surface‐Driven Strategy to Disrupt Globular Protein Binding While Aligning ECM for Controlled Cellular Activity

Selective protein adsorption on biomaterial surfaces is pivotal for regulating cell behavior and tissue organization in regenerative medicine. However, conventional 2D culture platforms fail to replicate the aligned architecture characteristic of vascular tissues. This study investigates whether a poly (vinyl alcohol)-stearate (PVA-stearate) surface coating can differentially modulate protein adsorption to direct extracellular matrix (ECM) assembly and cell alignment. The PVA-stearate conjugate was synthesized via esterification and extensively characterized by XRD, DSC, TGA, FTIR, AFM, and XPS, confirming successful chemical integration and a uniform nanoscale topography with moderate roughness compared to uncoated controls. Protein interaction analyses (MALDI-TOF and BCA assays) revealed selective suppression of non-specific globular protein adsorption (albumin, insulin) while facilitating collagen fibrillar assembly. Fibroblast (L929) cultures on the modified surfaces exhibited delayed initial adhesion followed by progressive elongation, unidirectional alignment, and coordinated cytoskeletal organization within 48 h, whereas unmodified substrates supported random orientation and disordered ECM deposition. These findings demonstrate that the PVA-stearate coating functions as a bioinstructive interface, enabling protein-specific modulation and guiding biomimetic cell-ECM interactions. This scalable and fully synthetic approach offers promising applications in vascular tissue engineering, antifibrotic surface design, and regenerative medicine platforms requiring controlled cellular organization.