Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Thursday Speaker Abstracts

STEROID RING VIBRATIONS ELUCIDATE CHOLESTEROL'S INFLUENCE ON LIPID MEMBRANES Jason H. Hafner 1 ; Kyra R Birkenfeld 1 ; Mathieu L Simeral 1 ; 1 Rice University, Physics & Astronomy, Houston, TX, USA Cholesterol is a major component of the plasma membrane of animal cells that impacts membrane fluidity, permeability, and lateral organization. Despite its importance, the molecular mechanisms of cholesterol's many functions are not clearly understood. Our objective is to use cholesterol’s low-frequency molecular vibrations to determine its conformational structure in different lipid environments. This will reveal the molecular mechanism behind cholesterol’s effects on lipid membrane structure and order. The methodology employed is based on our recent discovery that a steroid ring vibration band from 300 – 650 cm -1 is sensitive to the conformational structure of cholesterol’s iso-octyl chain. The chain structures fall into ten types that depend on the pattern of trans/gauche dihedral angles around four bonds in the chain. Each structure type is a set of conformers with the chain set at a similar angle relative to the plane of the steroid rings. Through a comparison of measured and DFT-calculated Raman spectra, we recently showed that each structure type has a unique Raman spectrum in the 300 – 650 cm -1 band. The corresponding spectral types are sufficiently distinct that they can be used to fit experimentally measured Raman spectra of cholesterol to directly measure the distribution of conformers in a sample. This process was carried out for cholesterol in phospholipid vesicles with different degrees of acyl chain saturation: DPPC, POPC, and DOPC. The resulting cholesterol conformer distributions are distinct for each phospholipid species. In DPPC cholesterol has the largest fraction of straight chains, consistent with the order and saturation of that phospholipid. In DOPC, which is unsaturated and has the lowest order, cholesterol has a higher fraction of bent chain conformers. We conclude that the cholesterol chain structure responds to phospholipid saturation, with straighter cholesterol chains increasing the membrane thickness to influence lipid membrane properties.


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