Effect of phase transition on the distribution of membrane-associated particles in microsomes.

(1) Rat liver microsomes were studied by freeze-fracture electron microscopy. The distribution of membrane-associated particles indicated the right-side-out orientation of microsomal vesicles. Studies at different temperatures were performed. At 30 degrees C membrane-associated particles are randomly distributed on membrane A-faces, while aggregations of particles are observed at 4 degrees C. (2) Aggregation is dependent on the cooling rates. It can be prevented by shock-freezing. (3) Particle aggregation is also prevented by cholesterol, added to the microsomes in equal molar ratio to the microsomal phospholid content. (4) These findings suggest that particle aggregation is caused by a partial freezing-out of phospholipid molecules during the phase transition from the liquid-crystalline to the gel state. (5) The results are discussed with respect to an observed increase in activation energy of microsomal drug monooxygenation at lower temperature.