Tackling lipid diversity in membranes: the effect on membrane and protein functions

Poger D, Corbett MSP and Mark AE

School of Chemistry & Molecular Biosciences, The University of Queensland, Brisbane QLD 4072, Australia.

Biological membranes regulate a myriad of cellular processes through the modulation of essential properties such as membrane fluidity and the formation of lipid microdomains. Such differences in turn affect the function of membranes and membrane proteins. The chemical and structural diversity of lipids is only being uncovered. For example, the repertoire of lipids in bacterial membranes is much broader than in eukaryotic membranes. In many if not most bacteria, membrane lipids include branched-chain fatty acids. Hopanoids have been identified in a range of bacteria. Branched-chain fatty acids have been proposed to protect membranes against hostile conditions and hopanoids have long been hypothesised to be surrogates of sterols, but, in fact, little is known about their actual effect on membranes. Using atomistic simulations, I showed that the different types of branching and hopanoids have specific effects on membrane fluidity and structure that allow bacteria to finely tune the sensitivity of their membranes to the environment. Furthermore, branched-chain lipids could affect the activity of commonly used disinfectants such as triclosan and para-chloroxylenol on membranes by modulating the interaction of the biocides with lipids and how deep they could insert into a membrane. The membrane composition also plays a critical role in the function of proteins. In simulations of the type-I cytokine receptors for growth hormone (GHR), prolactin (PRLR) and erythropoietin (EPOR) embedded in membranes, the presence of cholesterol altered the behaviour of the transmembrane domains, suggesting a key role of cholesterol in the mechanical coupling of the receptors through the plasma membrane upon receptor activation. The lipid composition is thus critical in the function of membrane and membrane proteins.