Selective membrane wrapping on differently sized nanoparticles regulated by clathrin assembly: A computational model

Nanoparticles (NPs) enter cells via multiple pathways, all of which are NP size dependent. Previous studies indicated that the clathrin-mediated endocytosis has different selectivity for the NP size, but the regulatory mechanism remains unclear and difficult to study at the molecular scale in vivo. By means of computer simulation, here we design membrane wrapping on differently sized NPs with mimic clathrin assembly at the opposite membrane side. With relatively large NPs readily wrapped by a pure membrane as manifested, clathrin modulates the process and tunes the size selectivity. Although finite curvature can be generated by cage-like clathrin assembly to facilitate membrane wrapping on relatively small NPs, the clathrin assemblage has a certain range of size, which is mismatched with larger NPs. Besides, the local membrane patch is rigidified by clathrin to increase the barrier of membrane wrapping on larger NPs. Competition of these items determines whether membrane wrapping on NPs is promoted or suppressed, and can be tuned by the NP-membrane adhesion strength, clathrin concentration, and inter-NP distance. Our results highlight the significance of complex environment in altering the nature of NP interaction with cell membranes, and are expected to help design NPs for biomedical applications requiring precise control of NP uptake or cell membrane attachment.