Abstract
Purpose:
To construct and test a statistical-thermodynamic model of sphere mixtures having short-range attractions; to quantitatively relate measured light scattering cross sections (Rayleigh ratios) of concentrated mixtures of gamma and alpha crystallin to their molecular properties.
Methods:
We model the liquid structure and thermodynamic susceptibilities of multicomponent sphere mixtures, which have different diameters and pairwise, infinitely short-range attractions, and calculate the resulting Rayleigh ratios. The model includes (i) hard-sphere alpha-alpha interactions, (ii) short-range attractive plus hard-sphere gamma-gamma interactions, and (iii) short-range attractive plus hard-sphere alpha-gamma interactions.
Results:
The sticky-sphere mixture model quantitatively reproduces measured Rayleigh ratios of bovine alpha/gamma mixtures, from dilute concentrations where light scattering depends on molecular weights and virial coefficients, to high concentrations like those in the lens, where short-range order and phase separation occur. The model reproduces concave-up composition dependence and more complicated temperature-dependent Rayleigh ratio at high concentrations, and concave-down composition dependence at lower concentrations (Thurston GM, J. Chem. Phys. 124,134909 (2006)). It also models light scattering cross sections of alpha/gamma mixtures that include the cataractogenic human gammaD (HGD) mutant E107A, in terms of altered attractive HGD/alpha interactions (Banerjee PR, et al, PNAS 108(2): 574-579 (2011)).
Conclusions:
The present model provides a quantitative tool for studying effects of normal and altered molecular interactions on light scattering in lens protein mixtures. The model (i) describes light scattering resulting from the combination of hard-sphere alpha-alpha, attractive gamma-gamma, and attractive alpha-gamma interactions, including non-monotonic effects of the latter (Dorsaz N, et al, J. Phys. Chem. B 113:1693-1709 (2009)), (ii) shows that concentrated alpha/gamma mixture light scattering is substantially reduced by composition fluctuations that are nearly perpendicular to the index of refraction gradient, (iii) models how alpha crystallin's open quaternary structure reduces light scattering from alpha/gamma mixtures, and (iv) predicts that increased gamma-gamma attractions raise light scattering of alpha-gamma mixtures more rapidly than that of solutions of gamma alone.
Keywords: 488 crystallins •
445 cataract •
660 proteins encoded by disease genes