Effect of Cell Penetration Peptides on model membranes of different rigidities

CROSIO, MATÍAS A.; VIA, MATIAS ; DEL PÓPOLO, MATIO G.; WILKE, NATALIA

Ciudad de La Plata, Provincia de Bs. As.

Congreso; XLVII Reunión Anual de la Sociedad Argentina de Biofísica; 2018

Sociedad Argentina de Biofíica

Cell Penetration Peptides (CPPs) are short sequences of mainly cationic aminoacids, and are considered one of the most effective and promising vectors fordelivering cargoes inside cells, such as proteins, nanoparticles, or nucleic acids.However, details on how CPPs traverse cell membranes, or how their absorption isaffected by physiologically relevant parameters such as membrane composition,surface charge, and surface electrostatics remain a matter of debate.There are two main mechanisms by which CPPs are incorporated into the cellularinterior: endocytosis, a mechanism with energy cost; and diffusion through thelipid bilayer, a process called passive permeation or also direct translocation. Herewe tackle this last mechanism.The objective of this work was to test the interaction of a poly-arginine (KR9C) withlipid membranes of different composition, in order to evaluate the influence of themembrane fluidity, compresibility and rigidity. We studied the interaction of thepeptide using as model membranes Lagmuir monolayers, Large unilamellarvesicles (LUVs) and Giant Unilamellar vesicles (GUVs) using compositions in theliquid-desordered, liquid-ordered and solid phase states.It was possible to observe differences in the interaction of KR9C with severalmembranes. On one hand, monolayer studies showed in the lipid mixtures asynergistic effect, with a higher incorporation of the peptides inside the mixedmonolayers than in the pure lipid monolayers. On the other hand, differenceswere also observed in the interaction of the peptide with membranes of differentcomposition. Z-potential measurements showed a lower peptide/lipid ratio forsaturation for the more fluid membranes, while the more rigid membranes lysed atlower concentrations of the peptide.Our results indicate that interaction, incorporation and concomitant effect of CPPson membranes depends on the mechanical properties of the host membrane.