Unveiling an “Anchor and Brush” Nanostructure: Synergistic Co‐Assembly of Amyloid Lysozyme and Hydrophilic Poly(2‐ethyl‐2‐oxazoline) for Robust, Protein‐Resistant Membranes

ABSTRACT Membrane fouling during protein processing persists as a major challenge for the biopharmaceutical and food industries. To address this, we engineer a robust bio‐hybrid nanocoating through the synergistic co‐assembly of amyloid fibril lysozyme (Lyz) and hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEOX), drastically boosting the antifouling performance of polyethersulfone membranes. Molecular dynamics simulations, together with experimental evidence, indicate that the PEOX/Lyz nanocoating adopts an “anchor‐and‐brush” nanostructure, in which Lyz is preferentially anchored near the polyethersulfone (PES) substrate while PEOX is enriched at the surface. The optimized coating enables ultra‐low protein adsorption (1.7 µg/cm 2 ) and nearly complete flux recovery against variously charged proteins, demonstrating exceptional fouling resistance and easy‐cleaning capability that surpasses state‐of‐the‐art membranes. This superior performance stems from a synergistic mechanism: the formation of a thick hydration layer (∼9 nm) provides a physical barrier, while attenuated Lennard‐Jones and Coulombic interactions create a low adsorption energy landscape, collectively preventing stable protein attachment and ensuring highly reversible fouling. This work not only deciphers the molecular‐level co‐assembly pathway but also provides a versatile platform for designing high‐performance, durable antifouling membranes toward demanding applications.