Altered phospholipid-apoB-100 interactions and generation of extra membrane material in proteolysis-induced fusion of LDL particles

Lipid droplets and membrane material are produced in the extracellular matr ix of the arterial intima during atherogenesis, Both in vitro and in vivo e xperimentation suggests that fusion of modified LDL particles leads to form ation of such lipid droplets. Here we applied proton NMR spectroscopy to pr obe surface phospholipids phosphatidylcholine (PC) and sphingomyelin (SM) o f LDL particles during proteolytic degradation of apolipoprotein B-100 (apo B-100). Initiation of apoB-100 degradation was accompanied by the abruptly increased intensity of the choline -N(C (H) under bar (3))(3) resonance of PC molecules, indicating disruption of their interactions with apoB-100, Ho wever, subsequent particle fusion was accompanied by a steady decrease in t he intensity of the choline resonances of both PC and SM. Electron microsco py of the proteolyzed LDL revealed irregularly shaped multilamellar membran es attached to aggregates of fused particles. This suggests formation of me mbrane material with low hydration, in which some of the atomic motions are hindered. Characterization of the behavior of the surface lipids of LDL pa rticles during apoB-100 degradation and other types of LDL modification Mil l aid in understanding molecular mechanisms leading to fusion and generatio n of multilamellar membrane material in the arterial intima during atheroge nesis. - Pentikainen, M. O., M. T. Hyvonen, K. Oomi, T. Hevonoja, A. Korhon en, E. M. P. Lehtonen-Smeds, M. Ala-Korpela, and P. T. Kovanen. Altered pho spholipid-apoB-100 interactions and generation of extra membrane material i n proteolysis-induced fusion of LDL particles.