Adhesion Mechanisms of Amyloid-Like Oligomer Monolayers Enabling Stable Surface Modification for Inert Polymers.

Amyloid oligomers are intermediate aggregates of misfolded proteins that exhibit stronger cellular interactions and enhanced interfacial adhesion capabilities compared with protofibrils and mature fibrils. However, the molecular basis of their adhesion remains insufficiently understood because of their structural complexity and mutability. Here, we present a surface-induced oligomerization method for fabricating an amyloid-like oligomer monolayer (AOM). Owing to its well-defined structure, stability, and accessibility, AOM serves as an ideal model system for elucidating the adhesion mechanisms of amyloid oligomers. AOM demonstrated a 34-fold increase in adhesion strength relative to native lysozyme. Systematic adhesion analysis on chemically defined surfaces combined with molecular simulations uncovered that hydrophobic interactions and hydrogen bonding are the dominant contributors to adhesion, supported by electrostatic and van der Waals forces. Furthermore, AOM can be used as a universal surface modification platform, outperforming conventional techniques in terms of stability and reliability, particularly on inert polymer surfaces. Because of its biocompatibility, the AOM significantly enhances cell adhesion on diverse substrates, with improvements ranging from 1.8 to 32 times compared to blank substrates. Collectively, this work not only provides a strategy for mechanistic insight into oligomer-mediated adhesion but also establishes a robust bioinspired surface modification platform for advanced material applications.