Cholesterol in aqueous solution: hydrophobicity and self-association

Area of Science:

• Biochemistry
• Physical Chemistry
• Molecular Biophysics

Background:

• Cholesterol's hydrophobicity is crucial for its biological roles and interactions.
• Previous predictions of cholesterol's hydrophobicity were based on surface area calculations.
• Understanding sterol behavior in solution is key to comprehending lipid-protein and sterol-lipid interactions.

Purpose of the Study:

• To accurately determine the free energy of transfer for cholesterol monomers from water to organic solvents.
• To investigate the discrepancy between calculated and observed hydrophobicity of cholesterol.
• To explore the potential for self-association of cholesterol in micellar systems.

Main Methods:

• Measurement of free energies of transfer for cholesterol monomer.
• Thermodynamic analysis of previously reported micelle formation data.
• Calculation of specific attractive interactions between cholesterol monomers.

Main Results:

• Cholesterol's hydrophobicity is significantly lower than predicted by hydrophobic surface area.
• Unusual water molecule orientation at the solute surface may explain this reduced hydrophobicity.
• Specific attractive interactions of 2-4 kcal/mol between cholesterol monomers were calculated.

Conclusions:

• Cholesterol's hydrophobicity is influenced by factors beyond simple surface area, potentially including water structuring.
• The calculated attractive interactions support the possibility of cholesterol self-association.
• These findings have implications for understanding sterol behavior in complex biological systems like sterol-lipid complexes.