<p>Cell-surface polysaccharides are
essential to many aspects of physiology, serving as a highly-conserved
evolutionary feature of life and as an important part of the innate immune
system in mammals. Here, as simplified biophysical models of these
sugar-coatings, we present results of molecular dynamics simulations of
hyaluronic acid and heparin brushes that show important effects of ion-pairing,
water dielectric decrease, and co-ion exclusion. As in prior studies of
macromolecular crowding under physiologically-relevant salt concentrations, our
results show equilibria with electroneutrality attained through screening and
pairing of brush anionic charges by monovalent cations at atomistic detail. Most
surprising is the reversal of the Donnan potential obtained from both
nonpolarizable and Drude polarizable force fields, in contrast to what 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. Potassium and sodium pairing to glycosaminoglycan
carboxylates and sulfates show similar abundance of contact-pairing and
solvent-separated pairing. We conclude that 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. </p>