Ion Pairing and Dielectric Decrement in Glycosaminoglycan Brushes

Molecular dynamics simulations of hyaluronic acid and heparin brushes are presented that show important effects of ion-pairing, water dielectric decrease, and co-ion exclusion. Results show equilibria with electroneutrality attained through screening and pairing of brush anionic charges by cations. Most surprising is the reversal of the Donnan potential that would be expected based on electrostatic Boltzmann partitioning alone. Water dielectric decrement within the brush domain is also associated with Born hydration-driven cation exclusion from the brush. We observe that the primary partition energy attracting cations to attain brush electroneutrality is the ion-pairing or salt-bridge energy associated with cation-sulfate and cation-carboxylate solvent-separated and contact ion pairs. Potassium and sodium pairing to glycosaminoglycan carboxylates and sulfates consistently show similar abundance of contact-pairing and solvent-separated pairing. In these crowded macromolecular brushes, ion-pairing, Born-hydration, and electrostatic potential energies all contribute to attain electroneutrality and should therefore contribute in mean-field models to accurately represent brush electrostatics.