There is a marked hysteresis between the heating and cooling polymorphic ph
ase transition of anhydrous cholesterol. At a scan rate of 0.05 degrees C/m
in the difference in transition temperatures between heating and cooling sc
ans is similar to 10 degrees C, This phenomenon also occurs with mixtures o
f cholesterol with phosphatidylserine and can result in an underestimation
of the amount of crystalline cholesterol in a sample that has not been cool
ed sufficiently. With 1-palmitoyl-2-oleoyl phosphatidylserine and 1-stearoy
l-2-oleoyl phosphatidylserine the cholesterol crystallites form while the l
ipid remains in the L-alpha phase. Sonication of dimyristoyl phosphatidylse
rine with a 0.4 mol fraction cholesterol results in the loss of cholesterol
crystallite diffraction, but only a partial loss of the polymorphic transi
tion detected by calorimetry. We therefore conclude that the thermal histor
y of the sample can have profound effects on the appearance of the polymorp
hic phase transition of cholesterol by differential scanning calorimetry. D
epending on the morphology of the vesicles, diffraction methods may underev
aluate the amount of cholesterol crystallites present.