Alpha-Crystallin Association with the Model of Human and Animal Eye Lens-Lipid Membranes is Modulated by Surface Hydrophobicity of Membranes

Abstract

Purpose

This research aims to probe the interaction of α-crystallin with a model of human, porcine, and mouse lens-lipid membranes.

Methods

Cholesterol/model of human lens-lipid (Chol/MHLL), cholesterol/model of porcine lens-lipid (Chol/MPLL), and cholesterol/model of mouse lens-lipid (Chol/MMLL) membranes with 0–60 mol% Chol were prepared using the rapid solvent exchange method and probe-tip sonication. The hydrophobicity near the surface of model lens-lipid membranes and α-crystallin association with these membranes were investigated using the electron paramagnetic resonance spin-labeling approach.

Results

With increased Chol content, the hydrophobicity near the surface of Chol/MHLL, Chol/MPLL, and Chol/MMLL membranes, the maximum percentage of membrane surface occupied (MMSO) by α-crystallin, and the association constant (K_a) decreased, showing that surface hydrophobicity of model lens-lipid membranes modulated the α-crystallin association with these membranes. The different MMSO and K_a for different model lens-lipid membranes with different rates of decrease of MMSO and K_a with increased Chol content and decreased hydrophobicity near the surface of these membranes suggested that the lipid composition also modulates α-crystallin association with membranes. Despite different lipid compositions, complete inhibition of α-crystallin association with model lens-lipid membranes was observed at saturating Chol content forming cholesterol bilayer domains (CBDs) with the lowest hydrophobicity near the surface of these membranes. The decreased mobility parameter with increased α-crystallin concentration suggested that membranes near the surface became less mobile due to α-crystallin association. The decreased mobility parameter and increased maximum splitting with increased Chol content suggested that membranes became less mobile and more ordered near the surface with increased Chol content.

Conclusions

This study suggested that the interaction of α-crystallin with model lens-lipid membranes is hydrophobic. Furthermore, our data indicated that Chol and CBDs reduce α-crystallin association with lens membrane, likely increase α-crystallin concentration in lens cytoplasm, and possibly favor the chaperone-like activity of α-crystallin maintaining lens cytoplasm homeostasis.

Keywords:

• α-crystallin
• model lens-lipid membrane
• hydrophobic interaction
• cholesterol
• lens cytoplasm homeostasis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author, LM, upon reasonable request.

Additional information

Funding

This work was supported by the National Institutes of Health (USA) under Grant R01 EY030067.