1. A model for the effect of time-dependent macromolecular crowding upon the rate of protein fibrillation was developed and presented as a possible explanation for the similar age dependence of the appearance of diverse neurodegenerative diseases that are attributed to the aggregation or fibrillation of different proteins with very different intrinsic colloidal stabilities (A. Minton). 2. An equilibrium model for the combined effect of macromolecular crowding and surface adsorption upon protein fibrillation was developed. The model predicts a highly cooperative transition between a slightly self-associating tracer species in bulk solution and a highly self-associated adsorbed tracer. Model estimates of the tendency of linear oligomers of various sizes to adsorb in the presence of unreactive crowders occupying various fractions of total solution volume are compared with the results of Monte Carlo simulations (T. Hoppe, A. Minton) 3. The effect of several monosaccharides and oligosaccharides on the thermal stability of two proteins (alpha-lactalbumin and lysozyme) at pH 7 has been measured via the temperature dependence of absorbance and ellipticity. The effect per mole of three monosaccharides on the free energy of unfolding is indistinguishable, that of two disaccharides approximately twice as large, that of a trisaccharide approximately three times as large and that of a tetrasaccharide approximately four times as much. The data were accounted for quantitatively by a simple statistical-thermodynamic model in which the interaction between all sugars and both proteins is assumed to be essentially entirely due to steric repulsion. (F. Ahmad, I. Beg, A. Minton)
