Sum frequency spectroscopy studies on cell membrane fusion induced by divalent cations

Cell membrane fusion is a fundamental biological process involved in a number of cellular living functions. Regarding this, divalent cations can induce fusion of the lipid bilayers through binding and bridging of divalent cations to the charged lipids, thus leading to the cell membrane fusion. How-ever, the elaborate mechanism of cell membrane fusion induced by divalent cations is still needed to be elucidated. Here, surface/interface sensitive sum frequency generation vibrational spectroscopy (SFG-VS) and dynamic light scattering (DLS) were applied in this research to study the responses of phospholipid monolayer to the exposure of divalent metal ions i.e. Ca²⁺ and Mg²⁺. According to the particle size distribution results measured by DLS experiments, it was found that Ca²⁺ could induce inter-vesicular fusion while Mg²⁺ could not. An octadecyltrichlorosilane self-assembled monolayer (OTS SAM)-lipid monolayer system was designed to model the cell membrane for the SFG-VS experiment. Ca²⁺ could interact with the lipid PO₂⁻ head groups more strongly, resulting in cell membrane fusion more easily, in comparison with Mg²⁺. No specific interaction between the two metal cations and the C=O groups was observed. However, the C=O orientations changed more after Ca²⁺-PO₂⁻ binding than Mg²⁺ mediation on lipid monolayer. Meanwhile, Ca²⁺ could induce dehydration of the lipids (which should be related to the strong Ca²⁺-PO₂⁻ interaction), leading to the reduced hindrance for cell membrane fusion.