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

VIA, MATÍAS A.; DEL PÓPOLO, MARIO G.; MAYORGA, LUIS S.; WILKE, NATALIA

SOFT MATTER

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2020 vol. 16 p. 9890 - 9898

1744-683X

Coarse-grained Molecular Dynamics simulations were performed to shed light on the arginine"magic", that gives polyarginine peptides a high CPP-effects. We calculated the free-energycosts associated with the internalization process of a nona-arginine (R9), chemically boundedto a polyglycine, which acts as a model hydrophilic cargo. By comparing the energy costs ofadsorption and insertion into an anionic membrane, we quantified the efficiency of R9 as a carrierof hydrophilic molecules through membranes. We also analyzed the effect of modifying thetype and concentration of anionic lipids in the bilayer, and the implication of these factors in thetrafficking of the R9G9 complex compared to that of R9 and G9 separately. Of particular interestwas the evaluation of ionized palmitic acid (palmitate) as a catalyzer of the translocation of theCPP-cargo complex across lipid membranes. Finally, we addressed the influence of the size ofthe hydrophilic cargo over the adsorption/insertion process. We found that the insertion rate ofG31 was not enhanced by chemically coupling to R9. Our results prove that the CPP efficiency ofR9 as a carrier of a hydrophilic cargo could be enhanced by the presence of ionized fatty acids inthe membrane, and that it is dependant on the size of the hydrophilic cargo.