Thermodynamics and Kinetics of the Interactions Between Proteins and Hydrophilic Polymers

Hydrophilic polymers are being investigated as possible coating agents for therapeutic nanoparticles because of their capacity to reduce immune response and increase circulation life time. The mechanism of action of these coatings is not well understood although it is clear that they unspecifically reduce the amount of proteins adsorbing on the nanoparticle surface coming in contact with biological fluids. Here we have investigated, using state-of-the-art atomistic molecular dynamics simulations, the equilibrium and kinetic properties of the interactions forming between human serum albumin, the most abundant protein in the blood stream, and two different and promising polymers poly(ethylene glycol) and poly-sarcosine and we have compared the results with a polymer which is an isomer of poly-sarcosine but has a totally different behavior in terms of adsorption, poly-alanine, because of its well-known aggregation propensity. The results show how the two hydrophilic polymers have a very similar behavior in terms of the amount of polymers adsorbed on the protein surface, pattern of interactions and the kinetics of the adsorption process, with differences emerging due to the different flexibility of the two molecules. In contrast poly-alanine adsorbs significantly more strongly on the protein surface, with a slower kinetics, and a quantitatively, but not qualitatively, different interaction pattern with the surface amino acids with respect to the hydrophilic polymers.