Poly-Sarcosine and Poly(ethylene-glycol) interactions with proteins investigated using molecular dynamics simulations

TL;DR

This study uses molecular dynamics simulations to compare how poly-sarcosine and poly(ethylene-glycol) interact with serum albumin, revealing similar affinities and insights into polymer-water-protein interactions relevant for nanoparticle biocompatibility.

Contribution

It provides the first detailed comparison of poly-sarcosine and PEG interactions with a key serum protein using molecular dynamics simulations.

Findings

Poly-sarcosine and PEG have similar affinity for serum albumin surface.

Minor differences in adsorption layer thickness relate to polymer flexibility.

Poly-alanine shows higher affinity due to different water interactions.

Abstract

Nanoparticles coated with hydrophilic polymers often show a reduction in unspecific interactions with the biological environment, which improves their biocompatibility. The molecular determinants of this reduction are not very well understood yet, and their knowledge may help improving nanoparticle design. Here we address, using molecular dynamics simulations, the interactions of human serum albumin, the most abundant serum protein, with two promising hydrophilic polymers used for the coating of therapeutic nanoparticles, poly(ethylene-glycol) and poly-sarcosine. By simulating the protein immersed in a polymer-water mixture, we show that the two polymers have a very similar affinity for the protein surface, both in terms of the amount of polymer adsorbed and also in terms of the type of amino acids mainly involved in the interactions. We further analyze the kinetics of adsorption and how it affects the polymer conformations. Minor differences between the polymers are observed in the thickness of the adsorption layer, that are related to the different degree of flexibility of the two molecules. In comparison poly-alanine, an isomer of poly-sarcosine known to self-aggregate and induce protein aggregation, shows a significantly larger affinity for the protein surface than PEG and PSar, which we show to be related not to a different patterns of interactions with the protein surface, but to the different way the polymer interacts with water.