LAUSR

Cardiolipin is a unique lipid molecule, which has an unusual dimeric structure with a dual-phosphate headgroup and four acyl chains. In most eukaryotic membranes cardiolipin is absent or present only at very low concentrations, however in the inner mitochondrial membrane (IMM) cardiolipin constitutes approximately 10-20% the lipid composition. Cardiolipin is believed to play a role the organization and morphology of the IMM, which contains highly curved membrane regions called cristae that protrude into the matrix. Cardiolipin is also involved in cellular respiration and apoptosis, and has been shown to bind preferentially to several mitochondrial integral and peripheral proteins. During its biosynthesis in the IMM, cardiolipin undergoes a remodeling process whereby acyl chains are removed and replaced to produce mature cardiolipin species with highly unsaturated and uniform lipid tail composition. In the mitochondrial disorder Barth syndrome, defects in the remodeling machinery lead to accumulation of the three-tailed cardiolipin variant monolysocardiolipin. The phenotype of Barth syndrome cells includes abnormal mitochondrial morphology and inhibited energy metabolism. In this work we explore the relationship between the spatial distribution of lipid species and membrane curvature in cardiolipin containing heterogeneous membranes using molecular dynamics simulations. We investigate cardiolipin-containing bilayer properties both in flat lamellar environments and in highly curved (buckled) membranes, and demonstrate that clustering of cardiolipin occurs in areas of high negative curvature. We compare this clustering behavior as well as the pressure induced buckling susceptibility and other biophysical membrane properties in several bilayer systems. One goal of this study is to elucidate the effect of an accumulation of monolysocardiolipin on the physical properties of lipid bilayers.