pH-responsive dendrimers interacting with lipid membranes

Simulations were performed to study the dendrimer-lipid membrane interactions in the context of gene delivery systems via exploring the influence of various pH values. As the pH decreases, dendrimers will adsorb on the negatively charged lipid bilayer, and even induce a hole formation on the membrane. We suggest the fourth generation of dendrimers to be the best candidate for gene delivery because of its low toxicity and high efficiency. Additionally, the hole formation under low pH conditions could lead to an asymmetrical bilayer because it facilitates the flip of the negatively charged lipids in one leaflet of the bilayer. We highlight the importance of the regulable electrostatic interaction by biologically relevant stimuli around the lipid membrane.