From Lanosterol to Cholesterol: Structural Evolution and Differential Effects on Lipid Bilayers

Abstract

Cholesterol is an important molecular component of the plasma membranes of mammalian cells. Its precursor in the sterol biosynthetic pathway, lanosterol, has been argued by Konrad Bloch (Bloch, K. 1965. Science. 150:19-28; 1983. CRC Crit. Rev. Biochem. 14:47-92; 1994. Blonds in Venetian Paintings, the Nine-Banded Armadillo, and Other Essays in Biochemistry. Yale University Press, New Haven, CT.) to also be a precursor in the molecular evolution of cholesterol. We present a comparative study of the effects of cholesterol and lanosterol on molecular conformational order and phase equilibria of lipid-bilayer membranes. By using deuterium NMR spectroscopy on multilamellar lipid-sterol systems in combination with Monte Carlo simulations of microscopic models of lipid-sterol interactions, we demonstrate that the evolution in the molecular chemistry from lanosterol to cholesterol is manifested in the model lipid-sterol membranes by an increase in the ability of the sterols to promote and stabilize a particular membrane phase, the liquid-ordered phase, and to induce collective order in the acyl-chain conformations of lipid molecules. We also discuss the biological relevance of our results, in particular in the context of membrane domains and rafts.

Influence of cholesterol on the structure of stratum corneum lipid model membrane

“…This statement is also in agreement with the generally accepted hypothesis for phospholipid membranes showing that CHOL tends to increase the thickness and decrease the fluidity and permeability of the lipid bilayers in the fluid phase [48][49][50]. The effect can be explained taking into account that CHOL increases the conformational order of the hydrocarbon chains of the other lipids, which causes the chain mobility and the membrane fluidity to decrease.…”

“…In the case of phospholipid membranes, this effect has been explained by CHOL dual act of inducing high conformational order in the lipid chains and, simultaneously, breaking the lateral packing order of the lipid molecules. As a result, CHOL facilitates formation of the liquid ordered phase in phospholipid bilayers [50,55]. Possibly, CHOL can influence the SC lipid membranes in a similar way.…”

Advanced Instrumentation of Frequency Modulation AFM for Subnanometer-Scale 2D/3D Measurements at Solid-Liquid Interfaces

“…5(b). So far, such a linear arrangement of the inserted cholesterols has been tentatively suggested by some of the simulation studies as a possible short-range ordering [62]. Although 50% molar content of cholesterol is much larger than that in the physiological conditions, our result clarified that the DPPC-cholesterol mixture favors such an arrangement when sufficient number of cholesterols exist in the local area of lipid bilayer.…”

The effects of cholesterol and β-sitosterol on the structure of saturated diacylphosphatidylcholine bilayers

“…The increase of the thickness of DPPC or DMPC bilayers at t [ t m as an effect of cholesterol can be explained by the known ability of cholesterol to suppress trans-gauche isomerisation of saturated phosphatidylcholine chains in their fluid state (Korstanje et al 1990;Kusumi et al 1986;Marsh and Smith 1973;Miao et al 2002;Mouritsen and Zuckermann 2004;Schreier-Muccillo et al 1973;Urbina et al 1995;Vist and Davis 1990). Huang and Feigenson (1999) proposed the ''umbrella model'' as an explanation of this phenomenon.…”