Lysophospholipids as natural molecular harpoons sensing defects at lipid membranes

The conditions under which membranes composed of dimyristoyl, dipalmitoyl, and egg phosphatidylcholine (PC) are lysed by monomyristoylphosphatidylcholine monomer have been studied, The results indicate that dimyristoylphosphatidylcholine (DMPC) lipid bilayers in the gel state are lysed by lysoPC monomers. This propensity of the monomer is increased when the liposomes are shrunken by osmotic stress, However, the inclusion of cholesterol in gel-state membranes goes against this lytic action, In contrast, dipalmitoylphosphatidylcholine (DPPC) bilayers in the gel state are lysed at concentrations much higher than that corresponding to the critical micellar (CMC) concentration. The lytic concentration is drastically decreased to values below the CMC when DPPC bilayers are formed in the presence of disaccharides or when lateral groups are introduced in the fatty acid chain near the head group region. Bilayers in the fluid state incorporate lysoPC without breaking, However, they can be lysed by lysoPC monomers when they contain cholesterol or are dispersed in the presence of aqueous soluble proteins such as insulin and protease. A critical lyric concentration is defined in analogy to the critical micellar concentration. The free energy of membrane disruption is calculated from this concentration and compared with the free energy of lysoPC micelle formation for each of these conditions, The results indicate that lysoPC monomer acts as a molecular harpoon to sense defects in the molecular packing at the interface of the bilayers. (C) 1996 Academic Press, Inc.