Ion Pairing and Dielectric Decrement in Glycosaminoglycan Brushes

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 coion
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 the 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 pairings 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.