Nanoparticles modified with cell penetrating peptides: Assessing adsorption on membranes containing acidic lipids

CHIARPOTTI, MARÍA V.; LONGO, GABRIEL S.; DEL PÓPOLO, MARIO G.

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Año: 2021 vol. 197

0927-7765

Cell-penetrating peptides (CPP) are poly-cationic molecules that facilitate the cellular uptake of nano-sizedcargoes. Accumulation of the cargoes on the cell surface regulates the cargoes internalization rate and constitutesa critical step prior membrane crossing. In this work, we characterize the adsorption of nanoparticles coatedwith CPP on membranes containing acidic lipids. We describe how the particle-membrane interactions and theextent of adsorption, depend on the size of the particles, the number of grafted CPP molecules, and thecomposition of the solution in contact with the membrane. Our results are obtained by applying a moleculartheory that takes into account electrostatic and steric interactions, entropic effects, and the acid-base equilibriumof all titratable molecules. It also takes into account the shape, protonation state, charge distribution andconformational flexibility of the peptide-grafted particles. Adsorption free energy profiles allow to quantify theadsorption energy, and reveal that nanoparticles attachment and detachment from the membrane surface arerestrained by free energy barriers. At physiological pH, the surface binding of the nanoparticles is ultimatelydriven by the deprotonation of acidic lipids; the adsorption free energy is more sensitive to the concentration ofsalt or particles in solution than to the number of grafted CPP molecules. At variance, the height of theadsorption/desorption barriers increases with the CPP load. Our results indicate that electrostatic interactions,modulated by entropic effects, provide the driving force and regulate the adsorption kinetics of CPP-coatedparticles on acidic membranes.