Anomalous behavior of membrane fluidity caused by copper-copper bond coupled phospholipids

Abstract

Membrane fluidity, essential for cell functions, is obviously affected by copper, but the molecular mechanism is poorly understood. Here, we unexpectedly observed that a decrease in phospholipid (PL) bilayer fluidity caused by Cu was more significant than those by Zn and Ca, while a comparable reduction occurred in the last two ions. This finding disagrees with the placement in the periodic table of Cu just next to Zn and far from Ca. The physical nature was revealed to be an anomalous attraction between Cu cations, as well as the induced motif of two phospholipids coupled by Cu-Cu bond (PL-diCu-PL). Namely, upon Cu ion binding to a negatively charged phosphate group of lipid, Cu was reduced to Cu. The attraction of the cations then caused one Cu ion simultaneously binding to two lipids and another Cu, resulting in the formation of PL-diCu-PL structure. In contrast, this attraction cannot occur in the cases of Zn and Ca ions. Remarkably, besides lipids, the phosphate group also widely exists in other biological molecules, including DNA, RNA, ADP and ATP. Our findings thus provide a new view for understanding the biological functions of copper and the mechanism underlying copper-related diseases, as well as lipid assembly.

Copper blocks V‐ATPase activity and SNARE complex formation to inhibit yeast vacuole fusion

“…While kinetically separate, the effects of Cu 2+ on these functions could have a common origin such as the reduction of membrane fluidity. The mean by which Cu 2+ and not Zn 2+ or other metals (except for Ag 2+ ) alter membrane fluidity is due to copper‐copper interactions when bound to anionic phospholipids . The interaction with anionic phospholipids reduces Cu 2+ to Cu + which stabilizes the complex.…”

“…The mean by which Cu 2+ and not Zn 2+ or other metals (except for Ag 2+ ) alter membrane fluidity is due to copper-copper interactions when bound to anionic phospholipids. 46 The interaction with anionic phospholipids reduces Cu 2+ to Cu + which stabilizes the complex. This as other H + /V + -ATPases have been shown to be inhibited when membrane fluidity is reduced.…”

Membrane Rigidity and Phosphatidic Acid (PtdOH) Signal: Two Important Events in Acinetobacter guillouiae SFC 500‐1A Exposed to Chromium(VI) and Phenol

“…Conversely, the fact that A. guillouiae SFC 500‐1A is able to use phenol as a carbon source and thus completely degrade it (Ontañon et al, ) could explain why there were no changes in the physical state of the membrane under phenol treatment. Although various metals such as iron, chromium, copper, cadmium, mercury, and lead can induce rigidity in eukaryotic biological membranes (Amoruso et al, ; Boadi et al, ; Jiang et al, ; Karbownik et al, ; Ochoa et al, ), the effect of metals on bacterial membranes is not well known. However, aromatic compounds such as toluene, phenol, benzene, and catechol have been shown to produce a decrease in bacterial fluorescence polarization, which implies an increase in the fluidity of cell membranes (Bernal et al, ; Murínová et al, ).…”

“…Although various metals such as iron, chromium, copper, cadmium, mercury, and lead can induce rigidity in eukaryotic biological membranes (Amoruso et al, 1987;Boadi et al, 1992;Jiang et al, 2017;Karbownik et al, 2001;Ochoa et al, 2003), the effect of metals on bacterial membranes is not well known. However, aromatic compounds such as toluene, phenol, benzene, and catechol have been shown to produce a decrease in bacterial fluorescence polarization, which implies an increase in the fluidity of cell membranes (Bernal et al, 2007;Murínová et al, 2014).…”

Copper Blocks V-ATPase Activity and SNARE Complex Formation to Inhibit Yeast Vacuole Fusion

“…While kinetically separate, the effects of Cu 2+ on these functions could have a common origin such as the reduction of membrane fluidity. The mean by which Cu 2+ and not Zn 2+ or other metals (except for Ag 2+ ) alter membrane fluidity is due copper-copper interactions when bound to anionic phospholipids (36). The interaction with anionic phospholipids reduces Cu 2+ to Cu + which stabilizes the complex.…”