Nanopartículas de Oro Funcionalizadas con Péptidos de Penetración Celular -Síntesis, Caracterización e Interacción con Biomembranas-

BERBERIÁN M.V., MAYORGA L.S., CIOCCO ALOIA F. AND DEL PÓPOLO M.G.

Carlos Paz, Cordoba

Congreso; SAB 2013, XLII, Reunion Anual de la Sociedad de Biofisica de Argentina; 2013

Sociedad Argentina de Biofisica

Gold Nanoparticles Functionalized with Cell Penetrating Peptides -Synthesis, Characterization and Interaction with Biomembranes- Berberián M.V.1,2,  Mayorga L.S.2, Ciocco Aloia F. 1 and Del Popolo M.G1 Instituto de Ciencias Básicas (ICB)1 e Instituto de Histología y Embriología Mendoza (IHEM)2, Universidad Nacional de Cuyo, Mendoza, Argentina   Over the past decades nanoparticles (NP) have prompted a large amount of research in pharmaceutical sciences, as they offer novel alternatives in the design of drug delivery systems. It is noticeable, however, that despite the large body of bibliography in this area there is no consensus yet on the way NP are internalized and distributed within living cells. Size, shape and chemical composition of the surface are among the factors that control internalization rates. Experiments show that NP intake can occur through diffusion across the cell membrane, either mediated by the formation of a pore or the invagination of the lipid bilayer, or follow an endocytic pathway. In the present work we investigate the interaction of NP with the plasma membrane of living cells, and explore a possible non-endocytic internalization mechanism. We use human sperms as model cells. Gold NPs (10?100 nm) are synthesized by the reduction of HAuCl4 in sodium citrate, and the particle surface is subsequently covered with two different cell-penetrating peptides (CPP). The interaction of the functionalized NP with the sperms? membranes is monitored by electron microscopy. Our results indicate that, depending on the particle size, concentration, and incubation time, the NP show large affinity for the cell surface and are able to penetrate the plasma membrane, reaching the acrosome and the cell nucleus. In order to rationalize the interaction between the CPP-covered nanoparticles and the lipids of the cell surface, we have investigated by Molecular Dynamics simulations the adsorption and penetration of a standard CPP molecule (Arg9) into a model lipid bilayer (DPPC). Simulations predict a strong a binding energy to the lipid surface, while the penetration of the CPP into the membrane core is accompanied by the formation of a water channel.