Computer simulations of the interactions of high-generation polyamidoamine dendrimers with electronegative membranes

Abstract

Coarse-grained molecular dynamics simulations were performed to investigate the interactions of polyamidoamine dendrimers of generations 7, 8, and 9 with two types of negatively charged bilayers: one is a mixture of 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) in a ratio of 3 : 7, and the other is a pure DMPG bilayer. We find that in both cases the configuration of high-generation dendrimers only shows a very slight change. Furthermore, a raft-like domain composed of DMPG lipids forms as the mixed bilayer gradually wraps the high-generation dendrimers. On the other hand, for the pure DMPG bilayer with defects, the higher the dendrimer generation is, the faster the lipids are removed from the bilayer due to the stronger electrostatic attraction, and the larger the preexisted pore becomes. Moreover, we find that the defect in our simulations is responsible for the formation of a dendrimer-encased vesicle accompanied with the lipid flipping and dendrimer rotation. The size and lipid number of the vesicle are found to be in good agreement with experimental results. We suggest that for high-generation dendrimers, it is acceptable that the removal mechanism of lipids was interpreted with the dendrimer-encased vesicle model.