Interaction of cell penetrating peptides with model membranes

MATÍAS VIA, MARIO G. DEL PÓPOLO, NATALIA WILKE

Tucumán

Congreso; Reunión conjunta: III LAFeBS, IX Iberoamerican Congress of Biophysics, XLV SAB.; 2016

penetratingpeptides, namely polyarginines [1-3] by means of both, experimentaland in silico methods. In the experiments, we analyzed the penetrationof the hydrophilic peptide KR9C into Langmuir monolayers offatty acids with different dipolar potentials, and also of anionic lipids(DMPG). The experimental results show that an increase in the chargedensity of the fatty acid monolayers (which is achieved by changing thesubphase pH) favored the incorporation of KR9C.This was observed inMA and PA monolayers (with pKa 6), while PFTD (pKa 0) [4]is charged in the whole pH range, showing a high peptide incorporation.Conversely, negative DMPG monolayers did not incorporate, eventhough the molecules are negatively charged.Regarding the influence of the surface potential on KR9C incorporationinto the monolayers, we found that the negative value observed inPFTD films is the main factor for the very high peptide incorporation determined in these monolayers. In this regard, simulation results alsoput forward that transmembrane potential has a substantial influence onKR9C insertion in the lipid bilayer hydrophobic core.In summary, our study demonstrates that the presence of fatty acids anda negative surface potential are two important factors in the incorporationof polyarginines into Langmuir monolayers. The negative surfacepotential would be involved in the first step of the peptide translocationprocess across cell membranes, triggering the diffusion of the peptidetowards the water/lipid interface. Fatty acids incorporate substantiallymuch more peptide than DMPG, suggesting that the carboxyl groupsmight be relevant for the mechanism