Efficient and selective gas transport across soft and nonporous interfaces remains a pivotal challenge for biomimetic membrane design, particularly in extracorporeal membrane oxygenation (ECMO) systems. Here, we report a molecular-level mechanism by which interfacial confinement and protein assembly cooperatively induce CO2 selective transport in EAS (a class I hydrophobin that forms functional amyloid fibrils)-modified poly(4-methyl-1-pentene) (PMP) membranes. By using all-atom molecular dynamics simulations combined with potential of mean force (PMF) analysis, we systematically investigate gas permeation across EAS hydrophobin monomers, dimers, and trimers adsorbed on pristine and hydroxylated PMP surfaces. We find that oligomerization of EAS proteins drives the formation of interconnected interfacial cavities, transforming isolated transport pathways into a percolated pathway network. This structural transition reshapes the free-energy landscape from a barrier-dominated profile to a multi-well topology. CO2 can be selectively stabilized along the permeation coordinate, while O2 transport remains governed by higher and more localized barriers. Importantly, surface hydroxylation further amplifies this effect by introducing polar interactions that act as a tunable parameter for modulating interfacial energetics and gas-protein coupling. These findings establish an interfacial confinement-induced transport mechanism in which gas selectivity emerges not from intrinsic pore size, but from the collective interplay of protein assembly, interfacial free volume, and molecular interactions. This work provides a general design principle for engineering bioinspired composite membranes with enhanced gas selectivity in ECMO and related gas-separation applications.
