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Graduate Defense: Geraline Trossi-Torres
October 3 @ 3:00 pm - 4:00 pm MDT
Title: Modulation of Alpha-Crystallin-Membrane Association by Phospholipid Acyl Chain Length and Degree of Unsaturation
Program: Master of Science in Biomolecular Sciences
Advisor: Dr. Laxman Mainali, Physics
Committee Members: Dr. Henry Charlier, Chemistry and Biochemistry, and Dr. Matthew Ferguson, Physics
Cataract is the leading cause of blindness worldwide. The only treatment for cataracts is the surgical removal of the cataractous lens and the replacement of an intraocular lens. With less availability of treatment and low income, the visual damage caused by cataracts can go untreated. The cataract may develop again after surgery, such as posterior capsule opacification. With age and cataracts, α-crystallin, a significant protein of the mammalian eye lens, is progressively associated with the eye lens membrane. The primary association sites of α-crystallin with the membranes are phospholipids. However, it is unclear if phospholipids’ acyl chain length and degree of unsaturation influence the α-crystallin association. We used the electron paramagnetic resonance (EPR) approach to investigate the association of α-crystallin with phosphatidylcholine (PC) membranes of different acyl chain lengths and degrees of unsaturation and with and without cholesterol (Chol). The association constant (Ka) of α-crystallin follows the trends, i.e., Ka (14:0–14:0 PC) > Ka (18:0–18:1 PC) > Ka (18:1–18:1 PC) ≈ Ka (16:0–20:4 PC) where the presence of Chol decreases Ka for all membranes. With an increase in α-crystallin concentration, the saturated and monounsaturated membranes rapidly become more immobilized near the headgroup regions than the polyunsaturated membranes. Our results directly correlate the mobility and order near the headgroup regions of the membrane with the Ka, with the less mobile and more ordered membrane having substantially higher Ka. Furthermore, our results show that the hydrophobicity near the headgroup regions of the membrane increases with the α-crystallin association, indicating that the α-crystallin-membrane association forms the hydrophobic barrier to the transport of polar and ionic molecules, supporting the barrier hypothesis in cataract development. Taken together, our findings clearly show how the changes in phospholipids’ acyl chain length and degree of unsaturation influence α-crystallin association with model membranes and provide insight for further investigations to examine how such changes in lipids in the eye lens membranes with age and cataracts modulate α-crystallin association with native membranes.