Interfacial Interactions of Nanoparticles and Molecular Nanostructures with Model Membrane Systems: Mechanisms, Methods, and Applications

This review surveys how nanoparticles and biomolecular nanosized structures interact with model membrane systems, and how these interfacial processes govern their performance in drug and gene delivery, antimicrobial strategies, biosensing, and nanotoxicology. The nanostructures covered include polymeric nanoparticles, lipid-based carriers, peptide nanostructures, dendrimers, and multifunctional hybrids. Model membranes span Langmuir monolayers, supported lipid bilayers, vesicles/liposomes across sizes, and emerging hybrid or asymmetric constructs that better approximate native complexity. Mechanistically, interactions follow recurrent routes-surface adsorption, bilayer insertion, pore formation, and lipid extraction/reorganization-regulated by particle size, morphology, charge, ligand architecture, and lipophilicity, in conjunction with membrane composition, phase state, curvature, and asymmetry. A multiscale toolkit links structure, mechanics, and dynamics: Langmuir troughs and Brewster Angle Microscopy map thermodynamics and mesoscale morphology; atomic force microscopy and quartz crystal microbalance with dissipation resolve nanoscale topography and viscoelasticity; fluorescence microscopy/spectroscopy reports on localization and packing; neutron and X-ray reflectometry quantify vertical structure; molecular dynamics provides atomistic pathways and design hypotheses. Historically, the field advanced from early monolayers and bilayers, through the fluid mosaic model, to raft microdomains and modern biomimetic systems, enabling increasingly realistic experiments. Key advances include cross-method integration linking experimental observations with image-based computational models; persistent debates concern the translation from simplified models to living membranes, the role of dynamic coronas, and scale/force-field limits in simulations. Future efforts should prioritize hybrid models incorporating proteins and asymmetric lipidomes, standardized reporting and reference systems, rigorous coupling of experiments with calibrated simulations and machine learning, and alignment with safety-by-design and regulatory expectations, thereby shifting interfacial measurements from descriptive observation to predictive design rules.