How Glycine Betaine Modifies Lipid Membrane Interactions

Abstract

Ubiquitous in the cellular milieu, small organic compounds termed osmolytes help to regulate the response to environmental stress. Elasmobranchii, such as sharks, accumulate high concentrations of several osmolytes, most notably urea, trimethylamine N‐oxide (TMAO), and glycine betaine (GB). These three compounds are used to osmoregulate the organism's body fluids, so that they counteract seawater salinity, as well as the destabilizing effects of hydrostatic pressure on cells and their molecular components. Herein we focus on glycine betaine and show how it modifies interactions between lipid membranes. We find that the addition of GB exerts an apparent attractive force that draws neighboring membranes toward one another. We show that, at the molecular level, this apparent attraction between membranes in the presence of GB is due to its preferential exclusion from the space between adjacent membranes, which thereby exerts an osmotic pressure that brings membranes closer together. This action is similar to the one we have previously reported for TMAO. However, we find that the net effect of GB is significantly smaller than that of TMAO, because GB concomitantly significantly weakens van der Waals attractions between membranes by changing the dielectric properties of the intervening solution. Finally, we show how GB acts in combination with urea. At high total concentrations and over a wide range of GB‐to‐urea ratios, urea counteracts the effect of GB, so that the equilibrium separation between membranes is close to their values in pure water. This finding supports the prevailing idea that mixtures of several osmolytes can achieve minimal net impact on biomacromolecular stability while also counteracting osmotic stress.

Genomic insight into strategy, interaction and evolution of nitrifiers in metabolizing key labile-dissolved organic nitrogen in different environmental niches

“…watsonii C-113 own glycine betaine (GBT) transport gene opuD . GBT has been found common in bacteria as osmotic molecules ( Shakhman and Harries, 2021 ). A variety of soil and aquatic bacteria have catabolic pathways that convert choline to glycine in multiple steps via GBT ( Figure 1E ), using both choline and GBT as the sole carbon and nitrogen sources ( Wargo, 2013 ).…”

Solutions: how adaptive changes in cellular fluids enable marine life to cope with abiotic stressors

“…The addition of TMAO led to further increase in thickness, at least up to pressures of ~ 800 bar when the membrane as a whole entered a gel phase. A recent study of the effects of glycine betaine on model membranes showed that GB has effects similar to those of TMAO, albeit the strengths of the effects were generally lower (Shakhman and Harries 2021 ).…”

“…Therefore, the co-occurrence of urea and TMAO in elasmobranchs may help to thwart loss of optimal liquid–crystalline states in deep-living members of this group of fishes. In fact, in vitro studies using model membranes show that this type of counteracting solute effect does apply to membranes as well as to proteins (Shakhman and Harries 2021 ).…”