Interleaflet Decoupling in a Lipid Bilayer at Excess Cholesterol Probed by Spectroscopic Ellipsometry and Simulations

Area of Science:

• Biophysics
• Materials Science
• Computational Chemistry

Background:

• Supported lipid bilayers (SLBs) mimic cell membranes.
• Cholesterol significantly influences lipid bilayer phase behavior and biophysical properties.
• Understanding lipid-cholesterol interactions is crucial for membrane biophysics.

Purpose of the Study:

• To investigate the effect of excess cholesterol on 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) supported lipid bilayers.
• To explore cholesterol-induced changes in bilayer thickness, optical index, and stability.
• To demonstrate the utility of spectroscopic ellipsometry (SE) for studying lipid-cholesterol interactions.

Main Methods:

• Spectroscopic ellipsometry (SE) was used to measure changes in bilayer properties.
• Coarse-grained (CG) molecular dynamics (MD) simulations were performed to analyze bilayer structure and stability.
• DOPC:cholesterol mixtures at various ratios were simulated and analyzed.

Main Results:

• Cholesterol addition induced a condensation effect in SLBs up to 30% concentration.
• Excess cholesterol beyond 30% led to interleaflet decoupling and bilayer undulations.
• SE measurements revealed cholesterol's influence on bilayer thickness and optical index, indicating leaflet separation.

Conclusions:

• Cholesterol exhibits a concentration-dependent effect on DOPC SLBs, causing condensation and then decoupling.
• SE is a powerful technique for characterizing lipid-cholesterol interactions in artificial membranes.
• The findings provide insights into the role of cholesterol in modulating membrane biophysical properties.