Attractive Hydration Forces in DNA–Dendrimer Interactions on the Nanometer Scale

The energetic contribution of attractive hydration forces
arising
from water ordering is an interesting but often neglected aspect of
macromolecular interactions. Ordering effects of water can bring about
cooperativity in many intermolecular transactions, in both the short
and long range. Given its high charge density, this is of particular
importance for DNA. For instance, in nanotechnology, highly charged
dendrimers are used for DNA compaction and transfection. Hypothesizing
that water ordering and hydration forces should be maximal for DNA
complexes that show charge complementarity (positive–negative),
we present here an analysis of water ordering from molecular dynamics
simulations and free energy calculations of the interaction between
DNA and a nanoparticle with a high positive charge density. Our results
indicate not only that complexation of the dendrimer with DNA affects
the local water structure but also that ordered water molecules facilitate
long-range interactions between the molecules. This contributes significantly
to the free energy of binding of dendrimers to DNA and extends the
interaction well beyond the electrostatic range of the DNA. Such water
effects are of potentially substantial importance in cases when molecules
appear to recognize each other across sizable distances, or for which
kinetic rates are too fast to be due to pure diffusion. Our results
are in good agreement with experiments on the role of solvent in DNA
condensation by multivalent cations and exemplify a microscopic realization
of mean-field phenomenological theories for hydration forces between
mesoscopic surfaces.