Size, geometry and mobility of protein assemblage regulate the kinetics of membrane wrapping on nanoparticles

Understanding how nanoparticles (NPs) interact with cell membranes is of essential importance for developing nanomedicine and nanosafety evaluation. Such delicate process is regulated by the engineered NP properties and surface coatings, but also involves membrane-associated proteins that have been overlooked and yet to be elucidated. Given ubiquity and diversity of protein assembly occurring on the cell membrane, here we design three types of protein assemblage associated with the membrane, including the one-dimensional filament, two-dimensional mesh, and three-dimensional cage. Dissipative particle dynamics simulations are performed to investigate the NP-membrane interactions under different membrane confinement. Our results show the size dependent membrane wrapping on NPs regulated by the protein assemblage. Depending on the relative size, geometry and mobility of the protein assemblage, the induced membrane confinement either promotes or suppresses the membrane wrapping on NPs through competition of rigidifying the local membrane patch and inducing non-zero membrane curvature. When the normal wrapping is prohibited, membrane protrusions are triggered by the protein assemblage that assists the membrane wrapping on NPs from the top side. Then the NPs are trapped inside the membrane with failed internalization. This study will aid our understanding of the molecular mechanisms underlying the regulatory role of protein assemblage in the NP-cell membrane interactions. (C) 2021 Elsevier B.V. All rights reserved.