Enzymatic confinement in lipidic mesophases and liquid-crystalline nanoparticles: from nanostructure to biocatalytic function

Abstract Lipidic liquid-crystalline mesophases and their dispersed counterparts, lipid liquid-crystalline nanoparticles (LCNPs), constitute highly organized soft nanostructured materials that can accommodate biomolecules within both interconnected aqueous channels and lipid bilayers. Their internal architecture can be tuned over the nanometer scale, providing controlled microenvironments that regulate molecular transport, hydration, confinement, and interfacial interactions. These properties have established lipidic mesophases as versatile platforms for drug delivery and have also enabled new opportunities in biocatalysis, biosensing, membrane protein research, and functional nanobiotechnology. This review examines enzyme confinement in bulk lipidic mesophases and LCNPs from a biophysical perspective, relating mesophase structure to catalytic performance. We discuss how aqueous channel geometry, network topology, hydration, and lipid–protein interactions influence enzyme accommodation, diffusion, conformational stability, and activity. We further examine recent advances in enzyme-loaded lipidic systems, their emerging applications, and future opportunities in molecular bioeconomy and sustainable biorefineries. This body of evidence supports a conceptual framework in which enzyme behavior emerges from the combined influence of geometric constraints imposed by the aqueous network and physicochemical interactions at the enzyme–lipid interface.