Role of Cholesterol in Maintaining Lens Transparency

Abstract: The α-crystallin binding to the lens membrane increases with age and cataract with the corresponding decline of α-crystallin concentration in the cytoplasm. The lens membrane’s lipid composition and cholesterol (Chol) content changes drastically with age and cataract. The influence of changes in the lipid composition and Chol content in lens membranes in α-crystallin membrane binding is unclear. We have developed an electron paramagnetic resonance (EPR) spinlabeling and atomic force microscopy (AFM) approach to investigate the α-crystallin membrane binding and the physical properties of the membrane with α-crystallin binding. The physical properties include mobility, order, and hydrophobicity near the membrane surface with α-crystallin binding. The binding of the α-crystallin with membranes has been investigated in membranes made of individual lipid, two-component lipid mixtures, models of animal and human lens lipid membranes, and cortical and nuclear lens lipid membranes derived from a single lens. Our results show that lipid headgroup size and charge, hydrogen bonding between lipid headgroups, lipid curvature, acyl chain length, and degree of unsaturation modulate α-crystallin-membrane binding and the physical properties of membrane changes with α-crystallin binding. Moreover, our results show that independently of the lipid headgroup, acyl chain length, and degree of unsaturation, Chol and cholesterol bilayer domains (CBDs) inhibit α-crystallin membrane binding. However, the inhibition level differed depending on the lipid headgroup, chain length, and the degree of unsaturation. Furthermore, our data indicated that Chol and CBDs play a positive physiological role by preventing α-crystallin binding to lens membranes and possibly protecting against cataract formation and progression.

Bio:  Dr. Laxman Mainali is a tenure track Assistant Professor in the Department of Physics and faculty member of the Biomolecular Sciences PhD Program at Boise State University, working since the fall of 2019. Dr. Mainali is an experimental biophysicist whose research is funded by a $1.5 M NIH R01 grant focusing on understanding the mechanism and prevention of cataract development. Dr. Mainali has 44 publications in prestigious biophysical and ophthalmological journals, and his work was recognized by the International EPR Society’s John-Weil Young Investigator Award for outstanding contributions to the field. Today, he will present the recent findings from his lab about the positive physiological function of membrane cholesterol in an eye lens.