Adv Sci (Weinh). 2026 Jun 9:e76011. doi: 10.1002/advs.76011. Online ahead of print.
ABSTRACT
Integration of proteins into metal-organic frameworks (Protein@MOF) offers an effective strategy for protein stabilization across materials and biomedical applications. However, the molecular mechanism of protein-MOF interactions remains poorly understood, limiting rational control over their chemical and physical properties. Here, we develop a surfactant-guided strategy to modulate the assembly of protein@MOF through interfacial design. We discovered that the interfacial environment between proteins and MOFs is the dominant factor controlling encapsulation efficiency, structural integrity, and functional performance. Lipid-based non-ionic surfactants such as glycerol monooleate (GMO) increase the protein’s solvent-accessible surface area (SASA), suggesting partial remodeling of the protein surface and hydration shell. Interfacial GMO enhances protein encapsulation by 20% and accelerates MOF growth by 30%. Importantly, for horseradish peroxidase (HRP) encapsulated in MOF, incorporation of lecithin results in up to a six-fold enhancement in retained bioactivity and a near 60-fold increase in kcat. All-atom molecular dynamics simulations reveal concentration-dependent, domain-specific interactions between the surfactant and flexible surface residues via electrostatic and hydrophobic contacts. These findings establish surfactant-driven interfacial design as a general molecular strategy to enhance protein@MOF stability and function, enabling robust alternatives to lipid nanodiscs for membrane protein stabilization and advancing applications in biocatalysis, biosensing, and drug delivery.
PMID:42261836 | DOI:10.1002/advs.76011