The intermediate state of DMPG is stabilized by enhanced positive spontaneous curvature.

1,2-Dimyristoyl-sn-glycero-3-phospho-rac-glycerol (DMPG) at low salt concentrations has a complex endotherm with at least four components and extending over the span of 20 degrees. During this ongoing melting, the solution becomes viscous and scatters light poorly. This multipeak endotherm was suggested to result from the effects of curvature on the relative free energies of gel and fluid DMPG bilayers, further relating to the formation of an intermediate sponge phase between the lamellar gel and fluid phases. Although later studies appear to exclude a connected bilayer network, the relation of the endotherm peaks to curvature remains an appealing hypothesis. This was tested by including in the system both water-soluble small molecules (dimethyl sulfoxide, ethanol, and urea) as well as amphiphiles (myristoyl-lyso-PG, cholesterol, cholesterol-3-sulfate, and dimyristoylglycerol) known to alter the spontaneous curvature of bilayers. All compounds increasing the monolayer positive spontaneous curvature (ethanol, urea, myristoyl-lyso-PG, cholesterol-3-sulfate) increased the temperature span of the intermediate state and elevated the temperature of its dissolution, while all compounds increasing the negative spontaneous curvature (dimethyl sulfoxide, cholesterol, dimyristoylglycerol) had the opposite effect, implying that the intermediate state contains a structure with positive curvature. The results support the view that the intermediate state consists of vesicles with a large number of holes. The viscosity increase could be related to vesicle expansion needed to accommodate the numerous holes.