Mammalian phospholipid homeostasis: evidence that membrane curvatureelastic stress drives homeoviscousadaptation in vivo

Several theories of phospholipid homeostasis have postulated that cellsregulate the molecular composition of their bilayer membranes, such that acommon biophysical membrane parameter is under homeostatic control.Two commonly cited theories are the intrinsic curvature hypothesis, whichstates that cells control membrane curvature elastic stress, and the theory ofhomeoviscous adaptation, which postulates cells control acyl chain packingorder (membrane order). In this paper, we present evidence from datadrivenmodelling studies that these two theories correlate in vivo.We estimatethe curvature elastic stress of mammalian cells to be 4-7 10212 N, a valuehigh enough to suggest that in mammalian cells the preservation of membraneorder arises through a mechanism where membrane curvature elastic stressis controlled. These results emerge from analysing the molecular contributionof individual phospholipids to both membrane order and curvature elasticstress in nearly 500 cellular compositionally diverse lipidomes. Our modelsuggests that the de novo synthesis of lipids is the dominant mechanism bywhich cells control curvature elastic stress and hence membrane orderin vivo. These results also suggest that cells can increase membrane curvatureelastic stress disproportionately to membrane order by incorporatingpolyunsaturated fatty acids into lipids.