Extracting lipid vesicles from plasma membranes via self-assembly of clathrin-inspired scaffolding nanoparticles

Single-cell analysis is a new and rapidly expanding field, the goal of which is obtaining fresh information from individual cells to understand the regulatory mechanisms of cell development and diseases. Conventional approaches generally rely on the cell lysis which, however, is destructive to cells and against multiple sampling from the living cell. Here, we propose and design a scaffolding nanoparticle (NP) system that enables us to sample cytoplasmic contents without rupturing the cellular membrane, by mimicking the unusual features of clathrin. Our simulation results reveal the design principles, following which scaffolding NPs can extract lipid vesicles from plasma membranes, with both the pathway and the mechanism resembling the clathrin-mediated endocytosis, i.e. multiple NPs deposit at the membrane, assembling into cage-like structures to deform the membrane into a vesicle shape. As important design parameters, the interaction between different NPs should be properly stronger than that between each NP and the membrane to ensure the cage formation, and optimal NP concentration and the membrane surface tension are also requisite for extracting lipid vesicles. Our results provide useful guidelines for design of bio-inspired scaffolding NPs as an intelligent machine for practical use in but not limited to the single-cell analysis.