Farnesol-DMPC phase behaviour: a H-NMR study

Involved in a number of diverse metabolic and functional contexts, farnesol is a central component of the mevalonate pathway, post-translationally attaches to proteins, and affects a number of other membrane-associated events. Despite farnesol's biological implications, a detailed analysis of how farnesol affects the physical properties and phase behaviour of lipid membranes is lacking. As ²H-NMR spectra are sensitive to molecular motions and acyl chain orientation, they can be used to measure the degree of molecular order present in the system. Also, since the ²H-NMR spectra of fluid and gel phase lipids are very different, they are sensitive probes of membrane phase equilibrium and can be used to determine fluid-gel phase boundaries. In this study, dimyristoyl phosphatidylcholine-d₅₄ (DMPC-d₅₄) bilayers containing varying concentrations of trans-trans farnesol (2.5-20.0 mol%) are investigated over a range of temperatures (8-30 °C). Analysis of these spectra has led to the construction of a farnesol-DMPC-d₅₄ temperature-composition plot. We show that increasing concentrations of farnesol induce a decrease in the fluid-gel phase transition temperature and promote fluid-gel coexistence. Interestingly, farnesol does not seem to affect the quadrupolar splittings (Δv_Q) in the fluid phase, i.e., the organization of farnesol within the bilayer and its interaction with phospholipids does not appreciably influence acyl chain order in the fluid phase.