Regulating lipid composition rationalizes acyl-tail saturation homeostasis in ectotherms

ABSTRACTCell membranes mainly consist of lipid bilayers with an actively regulated composition. The underlying processes are still poorly understood, in particular how the hundreds of components are controlled. Surprisingly, in recent experiments on ectotherms, the cholesterol fraction, along with un- and mono-saturated acyl tail fractions and demixing temperatures, was shown to increase with body temperature. We establish a model based on chemical reaction networks to study regulation of membranes, resulting in multiple semi-grand canonical ensembles. By running computer simulations, we show that higher cholesterol fractions correlate with lower degrees of unsaturation, ultimately controlling the composition of lipid tails. Cholesterol also dictates membrane viscosity and regulation of the latter implies that cholesterol must increase with temperature. Overall, our model proposes a different picture of lipid regulation, where components can be passively, instead of actively, regulated.SIGNIFICANCEIn this article, we propose a regulation model where only some of the components are actively regulated between membranes, while others are naturally balanced by chemical potentials. This model provides a rationale to recently measured puzzling trends in ectotherms, that is, increased plasma membrane cholesterol fraction with temperature. Here, we show that it is directly correlated with with acyl tail saturation and order parameter correlation length. Furthermore, we highlight the relation between cholesterol and membrane viscosity.