Mammalian phospholipid homeostasis: homeoviscous adaptation deconstructed by lipidomic data driven modelling.

One of the mostly widely cited theories of phospholipid homeostasis is the theory of homeoviscous adaptation (HVA). HVA states that cells maintain membrane order (frequently discussed in terms of membrane fluidity or viscosity) within tight conditions in response to environmental induced changes in membrane lipid composition. In this article we use data driven modelling to investigate membrane order, using methodology we previously developed to investigate another theory of phospholipid homeostasis, the intrinsic curvature hypothesis. A set of coarse-grain parameters emerge from our model which can be used to deconstruct the relative contribution of each component membrane phospholipid to net membrane order. Our results suggest, for the membranes in the mammalian cells we have studied, that a ratio control function can be used to model membrane order. Using asynchronous cell lines we quantify the relative contribution of around 130 lipid species to net membrane order, finding that around 16 of these phospholipid species have the greatest effect in vivo. Then using lipidomic data obtained from partially synchronised cultures of HeLa cells we are able to demonstrate that these same 16 lipid species drive the changes in membrane order observed around the cell cycle. Our findings in this study suggest, when compared with our previous work, that cells maintain both membrane order and membrane intrinsic curvature within tight conditions.