Cholesterol Conformational\nStructures in Phospholipid\nMembranes

Cholesterol\nis a major component of biomembranes that\nimpacts membrane\norder, permeability, and lateral organization, but the precise molecular\nmechanisms of cholesterol’s actions are still under investigation.\nDensity functional theory (DFT) calculations have opened the fingerprint\nvibration bands of large molecules to detailed spectral analysis.\nFor cholesterol, Raman spectral interpretation for conformational\nstructure and hydrogen bonding is now possible. Here, DFT calculations\nof cholesterol conformers identify 10 structure types that also have\nunique low-frequency Raman spectra. By fitting experimental spectra\nto these types, the distribution of cholesterol structures present\nin phospholipid (PL) membrane vesicles was measured. The distributions\nreveal that the cholesterol iso-octyl chain tends to align with saturated\nPL chains and shifts to a thermal distribution for unsaturated PL\nchains. The results agree with the templating effect of cholesterol\non PL membranes and show that the top of the iso-octyl chain is rigid\nlike the rings. It is also shown that the inclusion of water molecules\nhydrogen bonded to the cholesterol hydroxy group in the DFT calculations\nmay improve the spectral fitting for future studies.