期刊
BIOPHYSICAL JOURNAL
卷 97, 期 5, 页码 1398-1407出版社
CELL PRESS
DOI: 10.1016/j.bpj.2009.07.001
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类别
资金
- Fundacion Areces, Ministerio de Educacion y Ciencia [BFU 2008-01637]
- Basque Government [07/26]
- University of the Basque Country [GIU 06/42]
Sphingosine-1-phosphate (S1P) is currently considered to bean important signaling molecule in cell metabolism. We studied a number of relevant biophysical properties of S1P, using mainly Langmuir balance, differential scanning calorimetry, P-31-NMR, and infrared (IR) spectroscopy. We found that, at variance with other, structurally related sphingolipids that are very hydrophobic, S1P may occur in either an aqueous dispersion or a bilayer environment. S1P behaves in aqueous media as a soluble amphiphile, with a critical micelle concentration of approximate to 12 mu M. Micelles give rise to larger aggregates (in the micrometer size range) at and above a 1 mM concentration. The aggregates display a thermotropic transition at similar to 60 degrees C, presumably due to the formation of smaller structures at the higher temperatures. S1P can also be studied in mixtures with phospholipids. Studies with dielaidoylphosphatidylethanolamine (DEPE) or deuterated dipalmitoylphosphatidylcholine (DPPC) show that S1P modifies the gel-fluid transition of the glycerophospholipids, shifting it to lower temperatures and decreasing the transition enthalpy. Low (<10 mol%) concentrations of S1P also have a clear effect on the lamellar-to-inverted hexagonal transition of DEPE, i.e., they increase the transition temperature and stabilize the lamellar versus the inverted hexagonal phase. IR spectroscopy of natural S1P mixed with deuterated DPPC allows the independent observation of transitions in each molecule, and demonstrates the existence of molecular interactions between S1P and the phospholipid at the polar headgroup level that lead to increased hydration of the carbonyl group. The combination of calorimetric, IR, and NMR data allowed the construction of a temperature-composition diagram (partial phase diagram) to facilitate a comparative study of the properties of S1P and other related lipids (ceramide and sphingosine) in membranes. In conclusion, two important differences between S1P and ceramide are that S1P stabilizes the lipid bilayer structure, and physiologically relevant concentrations of S1P can exist dispersed in the cytosol.
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