The interfacial electrostatic potential modulates the insertion of cell-penetrating peptides into lipid bilayers

VIA, MATÍAS A.; KLUG, JOAQUÍN; WILKE, NATALIA; MAYORGA, LUIS S.; DEL PÓPOLO, M. G.

PHYSICAL CHEMISTRY CHEMICAL PHYSICS

ROYAL SOC CHEMISTRY

Año: 2018 vol. 20 p. 5180 - 5180

1463-9076

ell-penetrating peptides (CPP) are short sequences of cationic amino-acids that show a surprisingability to traverse lipid bilayers. CPP are considered to be some of the most effective vectors tointroduce membrane-impermeable cargos into cells, but the molecular basis of the membranetranslocation mechanisms and its dependence on relevant membrane physicochemical properties haveyet to be fully determined. In this paper we resort to Molecular Dynamics simulations and experimentsto investigate how the electrostatic potential across the lipid/water interface affects the insertion ofhydrophilic and amphipathic CPP into two-dimensional lipid structures. Simulations are used to quantifythe effect of the transmembrane potential on the free-energy profile associated with the transfer of theCPP across a neutral lipid bilayer. It is found that the electrostatic bias has a relatively small effect on thebinding of the peptides to the membrane surface, but that it significantly lowers the permeatio