Surface charge density and fatty acids enhance the membrane permeation rate of CPP-cargo complexes

M. VIA; N. WILKE; MAYORGA, LUIS S.; M. DEL POPOLO

SOFT MATTER

ROYAL SOC CHEMISTRY

Lugar: Cambridge; Año: 2020

1744-683X

he CPP-effect makes reference to the process by which the membrane translocation rate of a cargo is enhanced by chemical functionalization with cell-penetrating peptides (CPPs). In this work we combine a simple kinetic model with free-energy calculations to explore the energetic basis of the CPP-effect. Two polyglicines are selected as model hydrophilic cargoes, and nonaarginine as a prototypical CPP. We assess the cargo carrying efficiency of nona-arginine by comparing the adsorption and insertion energies of the cargoes, the cargo-free CPPs, and the CPPcargo complexes, into lipid membranes of varying composition. We also analyze the effect of modifying the type and concentration of anionic lipids, and the implication of these factors on the translocation rate of the CPP-cargo complex. Of particular interest is the evaluation of the catalytic role of palmitic acid (palmitate) as a promoter of the CPP-effect. We also analyse the influence of the size of the cargo on the membrane adsor