Biophysical Characterization of Polysialic Acid—Membrane Nanosystems

Polysialic acid (polySia) is a long, membrane-bound, polyanionic polymer (with the degree of polymerization, DP, up to 400) of negatively charged sialic acid monomers. Biological roles of polySia are based on its ability to modulate repulsive and attractive interactions, and its ability to modulate membrane surface charge density, pH at the membrane surface, and membrane potentials. PolySia is used in anti-bacterial and anti-cancer therapies, and in neural tissue repair. Hydrophobically-modified polySia chains can form nano-structures (micelles or liposomes) with high stability and low toxicity for drug delivery. The analysis, based on the Goldman-Hodgkin-Katz equation, of transmembrane potential changes resulting from trans-membrane translocation of polySia is described. Membrane electrical equivalent circuit can be applied to calculate polySia transmembrane fluxes. Both the surface potential (ψS) and the potassium diffusion potential (Δψdiff, calculated using the Nernst equation) can modulate polySia-mediated membrane interactions. Langmuir monolayer technique can be applied to determine the excess free energy of mixing, ΔGexc, of lipid components in the presence of polySia. The effect of polySia on the van’t Hoff enthalpy (ΔHVH) of the phase transition of lipid bilayer can be determined using fluorescence spectroscopy. The dissociation constant, KD, for polySia-liposome complex can be determined using polySia-to-membrane FRET spectroscopy.