Phosphatidylethanolamine Is a Key Regulator of Membrane Fluidity in Eukaryotic Cells

Abstract

Adequate membrane fluidity is required for a variety of key cellular processes and in particular for proper function of membrane proteins. In most eukaryotic cells, membrane fluidity is known to be regulated by fatty acid desaturation and cholesterol, although some cells, such as insect cells, are almost devoid of sterol synthesis. We show here that insect and mammalian cells present similar microviscosity at their respective physiological temperature. To investigate how both sterols and phospholipids control fluidity homeostasis, we quantified the lipidic composition of insect SF9 and mammalian HEK 293T cells under normal or sterol-modified condition. As expected, insect cells show minimal sterols compared with mammalian cells. A major difference is also observed in phospholipid content as the ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) is inverted (4 times higher in SF9 cells). In vitro studies in liposomes confirm that both cholesterol and PE can increase rigidity of the bilayer, suggesting that both can be used by cells to maintain membrane fluidity. We then show that exogenously increasing the cholesterol amount in SF9 membranes leads to a significant decrease in PE:PC ratio whereas decreasing cholesterol in HEK 293T cells using statin treatment leads to an increase in the PE:PC ratio. In all cases, the membrane fluidity is maintained, indicating that both cell types combine regulation by sterols and phospholipids to control proper membrane fluidity.

Inhibition of Bacterial Toxin Activity by the Nuclear Stain, DRAQ5™

“…Cells must maintain their membrane integrity and structure to function properly, and one way that they combat changes to membrane fluidity is to alter the membrane composition by adjusting the ratio of certain lipids, particularly cholesterol (to decrease fluidity) and phosphatidylethanolamine (PE, to increase fluidity) (Dawaliby et al , 2016). We have previously shown that, like other bacterial toxins, e.g., (Alonso et al , 2000; Boesze-Battaglia et al , 2009; Farrand et al , 2010; Lai et al , 2013; Maxfield and Tabas, 2005; Patel et al , 2002; Schwiering et al , 2013; Zitzer et al , 2001), LtxA requires cholesterol in the plasma membrane to bind and kill target cells (Brown et al , 2013; Brown et al , 2015; Fong et al , 2006).…”

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

“…The radius of spontaneous curvature of cholesterol is tightly negative (R 0 ¼ 220 Å ) [56] and hence in a bilayer arrangement, frustration of the spontaneous curvature of cholesterol is one mechanism through which membrane order might be controlled. This suggests that other lipids with negative spontaneous curvature will also increase membrane order when their curvature is frustrated, as a recent in vivo study that replaces cholesterol with PE indicates [59].…”

Membrane Lipid Replacement: Clinical Studies Using a Natural Medicine Approach to Restoring Membrane Function and Improving Health

“…PE depletion results in decreased transmembrane potential across the inner mitochondrial membrane, and this results in impaired mitochondrial function [54]. In addition, PE has been shown to be important in regulating membrane fluidity [55]. Fusion of phospholipid vesicles with organelles like mitochondria results in organelle swelling and dilution of membrane components that are normally compacted into dense super complex structures for maximal interactions [56].…”