The Journal of Biological Physics and Chemistry

Prions, plaques and polyelectrolytes

Philippa M. Wiggins

Department of Medicine, University of Auckland and Genesis Research and Development Corporation, Auckland, New Zealand

Water is assumed to have a simplified configuration with only two strengths of hydrogen bonds. It is also assumed that microdomains of high density water (HDW) and low density water (LDW) coexist throughout the liquid range of temperatures. Prions are predominantly hydrophobic proteins, which fold and are soluble in the mixture of HDW and LDW. We hypothesize that double layers of polyelectrolytes contain highly enriched HDW, which selectively sequesters prions in their extended unfolded state. Hydrophobic surfaces of prions lower the dielectric constant in the double layer and further enrich the water in HDW, so that it is sufficiently reactive to cleave the bond linking the charge group to the backbone of the polymer. A single prion released into normal water folds. But two unfolded prions released together aggregate and precipitate before there is time to fold. As destruction of sequestering sites proceeds, the probability that a single site harbours two prions grows and the number of aggregates grow. Damage is caused by loss of function of valuable polyelectrolytes and of other polymers and cells, which stick nonspecifically to the incompatible patches of surface presented to the solution by precipitated prions.

Keywords: compatible surfaces, high density water, low density water