Charged Dendrimers on Lipid Bilayer Membranes: Insight through Dissipative Particle Dynamics Simulations

Abstract

Understanding the interactions of dendrimers with biological membranes is of fundamental importance in determining their potential biomedical applications like drug delivery vehicles and gene therapeutic agents. Herein we perform systematically mesoscopic simulations to investigate the interactions and binding structures in complexes comprised of charged dendrimers with lipid bilayer membranes. For these purposes, various interaction strengths between the outer-dendrimer hydrophilic component and lipid heads and those between the inner-dendrimer hydrophobic component and lipid tails are used in the simulations. The external force is also induced into the complexes by stretching the membranes to examine the influence of the dendrimer binding on the stabilization of the lipid bilayer membranes. Our simulations demonstrate that the increasing attraction between outer dendrimer and lipid heads leads to wider spread of dendrimer along the membrane surface, while the attraction between the inner dendrimer and lipid tails has a great effect on the insertion of the dendrimer into the bilayer membrane. It is found that the dendrimer can induce a hole in the tense bilayer membrane at earlier time for a stronger attraction between the hydrophobic dendrimer component and lipid tails, which prompts the failure of the membrane affected by the external forces or surroundings. The findings could provide some guidelines for the design of the dendrimers with defined molecular architectures and prompt the understanding for the stabilization of the tense membranes and the potential cytotoxicity of the charged dendrimers in the dendrimer−lipid bilayer membrane complexes.