Decreased microviscosity of membrane lipids in leukemic cells: Two possible mechanisms

Abstract

Steady-state fluorescence polarization studies with the fluorescent lipid probe 1,6-diphenyl 1,3,5-hexatriene were done to determine the degree of microviscosity of cellular membrane lipids and serum lipoproteins in human normal donors and leukemic patients. The results show a marked decrease in microviscosity of cellular membrane lipids in both intact lymphocytes and isolated cellular plasma membranes obtained from leukemic patients in clinical relapse as compared to intact lymphocytes and isolated cellular plasma membranes obtained from normal donors and leukemic patients in complete clinical remission. Concomitant to these dynamic changes in cellular membrane lipids, the degree of microviscosity of lipids in the blood serum of leukemic patients in clinical relapse is markedly reduced as compared to serum obtained from normal donors and leukemic patients in complete clinical remission. Moreover, an in vitro incubation of leukemic lymphocytes with normal low density lipoproteins results in an increased microviscosity of cellular membrane lipids. In addition to the interrelation between cellular membrane lipids and serum lipoproteins, plasma membrane vesicles with a high degree of lipid microviscosity were isolated from the blood serum and pleural effusion of leukemic patients in clinical relapse. Such membrane vesicles could not be detected in normal serum. Therefore, we suggest that the two major mechanisms associated with the decreased microviscosity of membrane lipids in human leukemic cells are an abnormal exchange in lipids between the leukemic cell surface membrane and leukemic serum lipoproteins and an exfoliation of plasma membrane vesicles with a high degree of microviscosity from the cell surface of leukemic cells.The dynamic nature of a biological lipid complex can be quantitatively monitored by fluorescence polarization analysis with the aid of the fluorescent hydrocarbon probe 1,6-diphenyl 1,3,5-hexatriene (DPH) (1-7). From the recorded degree of fluorescence polarization, the degree of microviscosity of the analyzed sample can be estimated (8,9). Results obtained with this method have shown that the major parameter that determined the degree of microviscosity of lymphocyte membranes is the molar ratio of cholesterol to phospholipids, the two main lipid components of membranes in mammalian cells (10,11 the main characteristic that determines this dynamic difference originates from a significant decrease in the molar ratio of cholesterol to phospholipids in the plasma membrane lipid core of leukemic lymphocytes (10). Recently, two hypotheses have been advanced to explain these differences between normal and leukemic lymphocytes: exchange of lipids between cellular membranes and serum lipoproteins (1, 17), and exfoliation of plasma membrane vesicles from the leukemic cells with a high ratio of cholesterol to phospholipids (10, 18). Our main interest in the present study was to determine the degree of microviscosity of lymphocyte membrane lipids and of serum lipids in normal donors and leukem...

Membrane-Targeted Nanotherapy with Hybrid Liposomes for Tumor Cells Leading to Apoptosis

“…For example, the cell membranes of leukemia and lymphoma, which have less cholesterol and more unsaturated lipid contents in the cell membranes, showed higher fluidity as compared with those of normal lymphocytes. [1][2][3][4][5] Similar findings were observed for other cancer cell membranes. [6][7][8][9][10] The membrane dynamics with higher fluidity should be a fundamental property of cancer cells and closely related to the biological features of the proliferative potential, invasive potential, and metastatic ability.…”

Membrane dynamics in human leukemia and lymphoma cells

“…Hydrophobic regions of cell membranes were labeled for 30 min at 37°C with 2 FM l,ddiphenyl-1,3,5hexatriene (DPH) in phosphate buffers of different pH, as in [20]. Labeling was also carried out with DPH-phosphate buffer solutions containing either 2.5% glutaraldehyde, or 10 mM sodium azide, or 0.2% phenylmethylsuifanyl fluoride (PMSF).…”

“…Steady-state polarization (P) measurements were done at 37°C with a MV-1 Elscint instrument, as in [20]. For the excitation of DPH, a plane polarized 365 nm band generated from a 200 W mercury arc was employed.…”

Translocation of a hydrocarbon fluorescent probe between Epstein-Barr virus and lymphoid cells: An assay for early events in viral infection

“…Based on this assumption, fluorescence polarization analysis of DPH has been extensively used, in the last few years, to analyze the dynamic structural organization of lipids in cellular membranes (9)(10)(11) and viral envelopes (12,13). These studies have independently shown that the P values of DPHlabeled lymphoid cells are markedly lower (14,15) than those of DPH-labeled enveloped viruses (12,13). Moreover, it has also been shown that hydrophobic molecules such as cholesterol (16)(17)(18)(19) and DPH (20,21) Cells.…”

“…The degree of fluorescence polarization (P) of the DPH-labeled liposomes, viruses, and cells was determined with the aid of the Elscint MV-1 microviscosimeter as described (15,20), and the P value was recorded directly by the instrument according to the equation…”