Two sterols, two bilayers: insights on membrane structure from molecular dynamics

Abstract

Cholesterol (CHL) and ergosterol (ERG) are two predominant sterols in eukaryotic cells. The differences in their chemical structure can influence membrane structure and dynamics; this study discusses the effect CHL and ERG have on yeast membrane models with characteristic lipid composition for the endoplasmic reticulum (ER) and the trans-Golgi network (TGN) of yeast Saccharomyces cerevisiae. Molecular dynamics simulations were used to understand the atomic details of the sterols’ interaction with lipid bilayers that have both saturated and unsaturated tails as well as neutral and charged headgroups. Our models include phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol lipids to mimic the environment of the ER and TGN. The models for each organelle are identical, respectively, except for the sterol type. The overall surface area per lipid has no statistical difference between models for the same organelle, 63.6 ± 0.4 Å² in the ER and 60.9 ± 0.4 Å² in the TGN with either ERG or CHL. However, the compressibility modulus is approximately 30% lower in the models with ERG. We analyse this difference based on the sterols’ chemical structure and examine other membrane properties such as the lipid tails order parameters, bilayer thicknesses, sterol tilt angles and sterol spatial orientation with respect to the lipid tails to compare trends with existing data from simulation as well as experiment. This is the first study, to our knowledge, to examine the effect of sterol type on multi-lipid bilayer models with all-atom molecular dynamics.

Keywords:

• Molecular dynamics
• cholesterol
• ergosterol
• membrane properties

Abbreviations:

• CC = cross-chain
• CHL = cholesterol
• CI = confidence interval
• D_B = bilayer thickness
• D_C = half the hydrocarbon thickness
• D_HH = head-to-head distance
• EDP = electron density profile
• ER = endoplasmic reticulum
• ERG = ergosterol
• FA = fatty acid
• MD = molecular dynamics
• NMR = Nuclear Magnetic Resonance
• K_A = compressibility modulus
• L_d = liquid disordered
• L_o = liquid ordered
• OPM = orientation of proteins in membranes
• PA = phosphatidic acid
• PC = phosphatidylcholine
• PE = phosphatidylethanolamine
• PI = phosphatidylinositol
• PS = phosphatidylserine
• SA = surface area
• S_CD = deuterium order parameters
• TGN = trans-Golgi network