Cell-penetrating peptides (CPP) are short sequences of cationic amino-acids that show a surprising ability to traverse lipid bilayers. CPP are considered to be some of the most effective vectors to introduce membrane-impermeable cargos into cells, but the molecular basis of the membrane translocation mechanisms and its dependence on relevant membrane physicochemical properties have yet to be fully determined. In this paper we resort to Molecular Dynamics simulations and experiments to investigate how the electrostatic potential across the lipid/water interface affects the insertion of hydrophilic and amphipathic CPP into two-dimensional lipid structures. Simulations are used to quantify the effect of the transmembrane potential on the free-energy profile associated with the transfer of the CPP across a neutral lipid bilayer. It is found that the electrostatic bias has a relatively small effect on the binding of the peptides to the membrane surface, but that it significantly lowers the permeation barrier. A charge compensation mechanism, arising from the segregation of counter-ions while the peptide traverses the membrane, determines the shape and symmetry of the free-energy curves and underlines relevant mechanistic considerations. Langmuir monolayer experiments performed with a variety of amphiphiles model the incorporation of the CPP into the external membrane leaflet. It is shown that the dipole potential of the monolayer controls the extent of penetration of the CPP into the lipid aggregate, to a greater degree than its surface charge.

Oxidation of Si(111) surfaces is a procedure widely used for their further functionalization with 3-aminopropyltriethoxysilane (APTES). In the present work, the formation of silicon oxide is carried out by chemical and electrochemical oxidation of the hydrogenated-silicon surfaces, giving rise to Si-Ox Chem and Si-Ox Echem surfaces, respectively. Both surfaces are then functionalized with APTES solution to form an aminopropylsilane (APS) film, using two quite different concentrations of APTES (0.001 and 0.1% v/v), to compare two limiting situations. At the lowest APTES concentration, the comparison of the kinetics of gold nanoparticles (AuNPs) anchoring process on both surfaces is found to be quite different, not only in the initial rate of NPs anchoring but also in the maximum percentage of coverage. In contrast, the kinetics behavior is almost the same when the surfaces are modified with the highest APTES concentration, reaching the same value of surface coverage. The different or similar behavior of both surfaces is analyzed by a careful characterization of Si-Ox Chem and Si-Ox Echem surfaces using XP spectroscopy and AFM measurements, before and after APS functionalization. The significant differences in the surface roughness of the Si-Ox samples, together with the determination of the number of −NH 3 + moieties after silanization at both APTES concentrations, leads to the conclusion that the availability of −NH 3 + moieties is dependent on two factors: the roughness of the Si-Ox Chem and Si-Ox Echem surfaces as well as the concentration of the APTES solutions. When the APS layer is formed at the lowest APTES concentration, surface roughness controls the number of different types of nitrogen functional groups. In contrast, at the highest APTES concentration, the surface roughness does not have any significant role in the number of −NH 3 + moieties present on both surfaces. Because the kinetics of AuNPs anchoring depends mainly on the probability of interacting with the −NH 3 + groups, the above characterization allows us to explain in a consistent way the kinetics behavior observed for each particular condition of surface preparation.

Arginine molecules bind to a DPPC monolayer, altering the interfacial electrostatic potential and the lateral mobility of the lipids, while having little effect on the compression isotherm of the monolayer.

A reaction coordinate that can be used when investigating binding to dynamical surfaces with molecular dynamics is introduced. This coordinate measures the distance between the adsorbate and an isocontour in a density field. Furthermore, the coordinate is continuous so simulation biases that are a function of this coordinate can be added to the Hamiltonian to increase the rate of adsorption/desorption. The efficacy of this new coordinates is demonstrated by performing metadynamics simulations to measure the strength with which a hydrophilic nanoparticle binds to a lipid bilayer. An investigation of the binding mechanism that is performed using the coordinate demonstrates that the lipid bilayer undergoes a series of concerted changes in structure as the nanoparticle binds.