Multiscale Molecular Modeling to Reveal Interactions between the Atomic Force Microscopy Tip and Lipid Bilayer Stacks.

Knowledge of AFM tip and lipid bilayer stack interactions is essential for designing and developing nano- to mesoscale lipid constructs. In this study, a model was developed to reveal the complex molecular mechanism governing tip-lipid interactions. This complexity in the interaction forces during penetration leading to a disturbance of lipid bilayers is explored using coarse-grained MARTINI molecular dynamics simulations for a multibilayer 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) lipid system and an AFM tip apex. Force-distance profiles acquired during AFM tip penetration displayed a sawtooth pattern with a periodicity consistent with the bilayer thickness. This computation provides mechanistic insights into this process: a layer-by-layer penetration with distinct features in force-distance traces to specific molecular events such as climbing, adhesion, and compression. The outcomes benefit development of engineered lipid-based materials used in drug and vaccine delivery and fabrication of lipid-based nanodevices and biosensors.