Coarse-grained molecular dynamics simulation of dendrimer transmembrane transport with temperature-dependent membrane phase states

Abstract Nanoparticles (NPs) have found widespread applications in biomedical fields, where their transmembrane transport is a fundamental mass transfer problem involved due to the natural physical barrier-membrane. Various factors have significant effects on the NP-membrane interaction, including NP properties, membrane structures and environment temperature. The body can experience a wide temperature range under the physiological and pathological conditions, which has significant effect on the membrane phase (i.e., fluid phase and gel phase). Understanding the effects of membrane phase on NP transmembrane process is crucial for NP design and their biomedical applications. In this study, we performed coarse-grained molecular dynamics (CGMD) simulations to investigate interactions between dendrimer and asymmetric membrane with different phases and cholesterol concentrations. Our simulation results show that the dendrimer can absorb to the surface of membrane with gel phase, while the dendrimer can insert into the membrane with fluid phase. The membrane features including dense and ordered packing of lipids, small area per lipid, large membrane thickness and bending modulus in the gel phase, bring difficulties for the membrane curvature and dendrimer insertion. The cholesterol in the membrane can improve the dendrimer-membrane interaction in the gel phase. Our study can extend the understanding of the dendrimer-membrane interaction mechanism at the molecular level, which would provide suggestions for the drug delivery and nanomedicine development.