Reaction-Limited Fusion Mechanism of Zwitterionic Phospholipid Nanodiscs

Lipid-based bilayered nanodiscs can be self-assembled by a mixture of phospholipids in aqueous solutions. It has been reported that the nanodiscs grow (fuse) upon dilution via a small angle neutron scattering (SANS) study. In this presentation, we will evaluate the kinetics of zwitterionic nanodiscs made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2 –dihexanoyl-sn-glycero-3-phophocholine (DHPC) at a molar ratio of 3.2 upon dilution by free DHPC (pre-micellation) solutions of different concentrations using time-resolved dynamics light scattering (DLS).  The result shows that the growth rate of nanodisc induced by dilution strongly depends on the DHPC concentration, suggesting that the disc fusion process is controlled by the surrounding DHPC concentration in solutions. This result provides the direct evidence that the fusion of nanodiscs is attributed to disturbance of equilibration between the concentrations of DHPC in solution and nanodisc upon dilution. The equilibrium constant is also investigated to identify whether it is thermodynamically controlled. This result will be compared with that of charged nanodiscs consisting of DMPC, DHPC, and small amount of charged 1,2-dimyristoyl-sn-glycero-3-phospho-(1’-rac-glycerol) (DMPG) to further understand the charge effect on the fusion mechanism.