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 homeoviscousadaptation (HVA). HVA states that cells maintain membrane order (frequently discussed in terms ofmembranefluidity or viscosity) within tight conditions in response to environmental induced changes inmembrane 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 beused to deconstruct the relative contribution of each component membrane phospholipid to netmembrane order. Our results suggest, for the membranes in the mammalian cells we have studied, that aratio control function can be used to model membrane order. Using asynchronous cell lines we quantifythe relative contribution of around 130 lipid species to net membrane order,finding that around 16 ofthese phospholipid species have the greatest effect in vivo. Then using lipidomic data obtained frompartially synchronised cultures of HeLa cells we are able to demonstrate that these same 16 lipid speciesdrive the changes in membrane order observed around the cell cycle. Ourfindings in this study suggest,when compared with our previous work, that cells maintain both membrane order and membraneintrinsic curvature within tight conditions.