Anin vivoratio control mechanism for phospholipid homeostasis: evidence from lipidomic studies

Abstract

While it is widely accepted that the lipid composition of eukaryotic membranes is under homeostatic control, the mechanisms through which cells sense lipid composition are still the subject of debate. It has been postulated that membrane curvature elastic energy is the membrane property that is regulated by cells, and that lipid composition is maintained by a ratio control function derived from the concentrations of type II and type 0 lipids, weighted appropriately. We assess this proposal by seeking a signature of ratio control in quantified lipid composition data obtained by electrospray ionization mass spectrometry from over 40 independent asynchronous cell populations. Our approach revealed the existence of a universal 'pivot' lipid, which marks the boundary between type 0 lipids and type II lipids, and which is invariant between different cell types or cells grown under different conditions. The presence of such a pivot species is a distinctive signature of the operation in vivo, in human cell lines, of a control function that is consistent with the hypothesis that membrane elastic energy is homeostatically controlled.

Lipid Spontaneous Curvatures Estimated from Temperature-Dependent Changes in Inverse Hexagonal Phase Lattice Parameters: Effects of Metal Cations

“…Furthermore, for most biophysical studies of lipid-protein interactions 4,51 and computational models 8,9,52,53 that are based on spontaneous curvature and stored elastic energy the accuracy of our approach is sufficient. We also note that in the case of DOPE, multiple estimates of c 0 exist in the literature, using a variety of X-ray diffraction methods (each of which quotes small errors in the value of c 0 ), there is a spread of c 0 values from -0.43 nm -1 to -0.33 nm -1 (± 13% of the mean).…”

“…For example, curvature elastic stress, which arises from a system being forced to adopt a curvature that is different from c 0 , has been shown to modulate the activity of many membrane interacting proteins 3,4 and drives the folding of other membrane bound proteins 5,6 . These observations underpin the intrinsic curvature hypothesis, which postulates that cells regulate the composition of their biological membranes so that the net curvature elastic stress is under homeostatic control [7][8][9][10] .…”

Mammalian phospholipid homeostasis: evidence that membrane curvature elastic stress drives homeoviscous adaptation in vivo

“…Extensive details of how the control functions were parametrized and how the values of w ces and w dis were obtained have been published previously [20,46], as summarized in § §2.1-2.3. Figure 1 provides an overview of control mechanisms in phospholipid homeostasis and the importance of developing quantitative models to understand the role of lipids in health and the environment.…”

“…One of these was a ratio control mechanism for membrane disorder inspired by HVA [20] and the other was a ratio control mechanism derived from the intrinsic curvature hypothesis [46,47]. Both these studies used the lipidomes of HL60 and HeLa cells to construct a systems-level insight into the collective properties of cellular membranes through data-driven modelling, summarized in §1.2.…”

“…Our previous studies [20,46] gave two sets of coarse-grain parameters (w ces and w dis ) determined by data-driven modelling using the HL60 and HeLa cell lipidomes. These w ces and w dis parameters can be substituted, with new lipidomic data, into equation (1.1) to give p dis and p ces values for these new lipidomes.…”