Aggregation of nanoparticles regulated by mechanical properties of nanoparticle–membrane system

Abstract

The aggregation of nanoparticles (NPs) on the cell membrane is crucial for the cellular uptake process and has important biological implications in protein–membrane interactions. In this paper, we systematically investigate how the aggregation is regulated by the mechanical properties of the NP–membrane system, including the membrane tension, and the size and shape of the NPs. Results show that when NPs aggregate parallel to the cell membrane, increasing the membrane tension will modulate the membrane-mediated interaction between the NPs from attractive to attractive–repulsive and finally to purely repulsive. In contrast, the membrane-mediated interaction is attractive and independent of the membrane tension when the NPs aggregate to a tubular configuration. For the aggregation of NPs of different sizes, the large-size NP is wrapped to a greater extent than the small-size NP. For the aggregation of nonspherical NPs, low aspect ratio and weak NP–membrane adhesion strength lead to the side-to-side configuration, whereas a system with a high aspect ratio and strong NP–membrane adhesion strength prefers the tip-to-tip configuration. Importantly, NPs of different sizes and anisotropic shapes are found to facilitate the aggregation process by reducing the energy barrier that should be overcome during the aggregation. The results reveal the mechanism of the aggregation of NPs on the cell membrane and provide guidelines to the design of NP-based drug delivery systems.