Data Driven Modelling of Phospholipid Homeostasis
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Evidence suggests that in vivo phospholipid biosynthesis is under homeostatic control, although the biomembrane properties and control mechanisms that underpin lipid homeostasis are unknown. It is clear that phospholipid composition is not homeostatically controlled given the large number of different compositions that have been reported in vivo under different experimental conditions. In our work we treat phospholipid composition as a steady state equilibrium and use lipidomics to quantify different multiple steady state lipid compositions. Using data driven modelling we set up an algorithm to search for different biophysical membrane properties that might be in operation and hence conserved by different steady state lipid compositions. Surprisingly, our mathematical models suggest two ‘rival theories’ of phospholipid homeostasis are equally well evidenced. These are the intrinsic curvature hypothesis [1, 2], which suggests membrane stored elastic energy is regulated and the theory of homeoviscous adaptation [3], which suggests membrane order is regulated.

Our most recent work suggests that the cells can control membrane order by regulating stored elastic energy, sheding light on the mechanisms behind phospholipid homeostasis [4].

 

[1] Dymond, M. K., Hague, C. V, Postle, A. D., & Attard, G. S. (2013). An in vivo ratio control mechanism for phospholipid homeostasis: evidence from lipidomic studies. Journal of the Royal Society, Interface / the Royal Society, 10(80), 20120854. doi:10.1098/rsif.2012.0854

[2] Hague, C. V., Postle, A. D., Attard, G. S., & Dymond, M. K. (2013). Cell cycle dependent changes in membrane stored curvature elastic energy: evidence from lipidomic studies. Faraday Discussions, 161, 481. doi:10.1039/c2fd20078c

[3] Dymond M.K. Mammalian phospholipid homeostasis: Homeoviscous adaptation deconstructed by lipidomic data driven modelling. Chemistry and physics of lipids. 2015 Oct 31;191:136-46.

[4] Dymond, M.K., 2016. Mammalian phospholipid homeostasis: evidence that membrane curvature elastic stress drives homeoviscous adaptation in vivo. Journal of The Royal Society Interface, 13(121), p.20160228.