Aqueous suspensions of phospholipids, either synthetic or natural mixtures from cell membranes, have been used to study how membrane bilayers assemble. The studies are based on a theory which describes membrane bilayer assembly as a physicochemical process that occurs only at a critical point, the physiological temperature of the cell. The optimum conditions for membrane bilayer stability, a prerequisite for normal cellular function, occur at the critical point; membrane lipid composition and the critical temperature are interdependent. When either lipid composition or temperature deviate from the required critical conditions, the membrane bilayer becomes unstable and its structure degenerates with catastrophic consequences for the cell. This mechanism of pathogenesis has been successfully tested with neural tissue lipids from a patient with metachromatic leukodystrophy, a disease with a well-defined lipid defect. Thus, measurements of the critical conditions for membrane bilayer assembly appear to be relevant for identifying membrane lipid defects in cellular dysfunction. The relevance of this membrane destabilization mechanism in other diseases with obscure etiologies is presently being tested.
