When peptides tease membranes: a molecular dynamics investigation of cationic peptides on lipid bilayers

JOAQUIN PUCHOL; MATIAS VIA; GALASSI, VANESA; NATALIA WILKE; MARIO G DEL POPOLO

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica; 2022

Universidad Nacional de Rosario IBR-CONICET

Cationic polypeptides (CPs) are part of a large family of peptides that are capable ofpermeating cell membranes. Their positive electric charge and secondary structure maycontribute to their membrane-permeation activity, although many details of thepermeation mechanism remain unclear. Cell penetrating peptides (CPPs) andantimicrobial peptides (AMPs) share the capability to disrupt cell membranes. The firstones are rich in arginine and lysine sequences, of up to 20 amino acids, and are involvedin endogenous transport mechanisms and cellular transduction. On the other hand, AMPsare longer chains of up to 50 residues, also rich in hydrophobic amino-acids, thatparticipate in the immune response of plants and animals. Their action mechanisminvolves the absorption to the target membrane, and some of them acquire an alpha-helixstructure upon insertion, reminiscent of a corkscrew.CPs mildly perturb the structure of the bilayer as part of their adsorption and subsequentinsertion mechanism. In addition, the surface net charge and the type of lipids thatcompose the membrane modulate the peptide-membrane binding strength. In this workwe apply Molecular Dynamics simulations to characterize, structurally and energetically,the peptides-membranes interactions. Our models consist of bilayer patches with differentlipid composition in contact with cationic polypeptides. We use the MARTINI coarsegrained force field with nonaarginine (R9) and Polybia-MP1 as models of each type ofpeptide. As a first step, we focus on characterizing the interaction energy of Polybia-MP1,evidencing its capability to interact with anionic as well as zwitterionic membranes.Subsequently, the influence of the CPs on the membrane fluidity is assessed formembranes covered with R9. Capillary-waves analysis method, mean squareddisplacement and membrane curvature perturbation simulations are performed. Ourresults, along with previous results for R9, show that both cationic peptides preferablybind to anionic membranes, while Polybia-MP1 also binds to neutral membranes. Also, R9yields a fluidification of the membrane that may affect the translocation mechanism.AcknowldegmentsConsejo Interuniversitario NacionalSecretaría de Investigación, Internacional y Posgrado (UNCuyo)Consejo Nacional de Investigación Científica y TécnicaAgencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación.Cluste Toko (FCEN-UNCuyo) y Serafin (CCAD-UNC)