  Membrane fluidity, well-known to be essential for cell functions, is
obviously affected by copper. However, the underlying mechanism is still far
from being understood, especially on the atomic level. Here, we unexpectedly
observed that a decrease in phospholipid (PL) bilayer fluidity caused by Cu2+
was much more significant than those induced by Zn2+ and Ca2+, while a
comparable reduction occurred in the last two ions. This finding clearly
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 a special attraction
between Cu+ cations, which can induce a motif forming 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
special 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 due to their electron structure. Remarkably, besides lipids, the phosphate
group widely exists in other biological molecules, including DNA, RNA, ADP and
ATP, which would also induce the similar structure of Cu ions with the
molecules. Our findings thus provide a new view for understanding the
biological functions of copper and the mechanism underlying copper-related
diseases.
