Physico-chemical properties and organization of lipids in membranes: their possible role in myocardial injury

Abstract

Lipids in biological membranes are organized in a bilayer configuration in order to form a semi-permeable barrier. The lipids are freely mobile in the bilayer, which is denoted as "fluid" or liquid-crystalline. For plasma membranes it is assumed that the lipids are not homogeneously distributed over the two leaflets or monolayers. This so-called lipid asymmetry is established for the erythrocyte membrane. There it was found that phosphatidylserine (PS) and phosphatidylethanolamine (PE) are present exclusively and predominantly in the cytoplasmic leaflet, respectively. It is shown that isolated PE at physiological conditions forms a non-bilayer configuration the so-called hexagonal HII phase. Moreover, isolated PS can undergo a transition from the fluid into the solid state upon addition of calcium. In mixtures of PS and PE, calcium is able to induce fusion events, possibly formation of the HII phase and phase separation of solid PS. The physico-chemical behaviour of these phospholipids will be discussed in the light of the structural changes of the sarcolemma of heart muscle cells observed by freeze-fracturing and thin section electron microscopy after ischaemia, ischaemia and reperfusion and the calcium paradox. The lateral phase separation of intramembranous particle aggregation is explained as isothermic phase separation by H+ and calcium. The disruption of the sarcolemma by the formation of blebs (liposomal structures) is interpreted as a destabilization of the bilayer configuration since PE prefers the HII phase and thus induces uncontrolled fusion events. This all leads to an irreversible disruption of the sarcolemma.