Enhanced Permeability of Charged Dendrimers across Tense Lipid Bilayer Membranes

Dendrimers have successfully proved themselves as functional nanodevices for drug delivery because they can render drug molecules a greater water solubility, bioavailability, and biocompatibility. It has recently been suggested that the structural changes of cell membranes (e.g., local lipid density and actual pore or hole) could affect the permeability across them for dendrimers. However, to understand these effects requires direct measurements in a single cell and is thus very difficult and more challenging. Here we use mesoscopic simulations to investigate the tension-mediated complexes comprising charged dendrimers and lipid bilayer membranes. The structures of membranes are alternated by adjusting their surface tensions. Our simulations demonstrate that the permeability of charged dendrimers can be effectively enhanced in the tense membranes, and the permeability in the actual hole is several times higher than that in the lipid-poor section. The possible mechanism of charged dendrimer-induced pore nucleation in the tense membranes is evaluated. The findings have implications in tuning intracellular delivery rates and amounts in nanoscale complex and chemotherapeutics.