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

Xiankai Jiang,Yanwen Tan,Junhong Lü,Jinjin Zhang,Pei Li,Zhi Zhu,Xiaojuan Hu,Bo Zhou,Bo Song,Chao Chang

doi:10.1038/s41598-018-32322-4

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 Cu2+ was more significant than those by Zn2+ and Ca2+, 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 Cu2+ ion binding to a negatively charged phosphate group of lipid, Cu2+ 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.

Highlights

Proper fluidity of the biological membrane is critically essential for numerous cell functions, such as adapting to the thermal stress of the environment of the microorganism[1], the binding of peripheral proteins associated at the lipid surface[2], reaction rates of enzymes[1], and even cell signaling and phagocytosis[3]
We observed that the decrease of the PC/PG bilayer fluidity caused by Cu2+ ions was much more significant than those induced by Zn2+ and Ca2+ ions, while a comparable reduction occurred in the last two cases
A model of two phospholipids coupled by a Cu-Cu bond was built to explain the unexpected behavior of the bilayer fluidity induced by the Cu2+ ion

Summary

Introduction

Proper fluidity of the biological membrane is critically essential for numerous cell functions, such as adapting to the thermal stress of the environment of the microorganism[1], the binding of peripheral proteins associated at the lipid surface[2], reaction rates of enzymes[1], and even cell signaling and phagocytosis[3]. Cremer and his coworkers studied effects of the Cu2+ ion on a bilayer comprised of both phosphatidylcholine (PC) and phosphatidylserine (PS), and proposed that the ion was bound to PS20. This binding was only stable under basic conditions, but not at acidic pH values. It was suggested that Cu2+ could stably bind to the amine moieties of PE lipids, while other transition metal ions to PE bound in a similar manner All these Cu2+-lipid interactions relate to the existence of amine moiety in the headgroup of the lipid. Ångström-resolution atomic force microscope (AFM) imaging supported the formation of diCu coupled to two lipids

Methods

Results

Conclusion