title: Cholesterol-Ceramide Interactions in Phospholipid and Sphingolipid Bilayers As Observed by Positron Annihilation Lifetime Spectroscopy and Molecular Dynamics Simulations.
abstract: Free volume voids in lipid bilayers can be measured by positron annihilation lifetime spectroscopy (PALS). This technique has been applied, together with differential scanning calorimetry and molecular dynamics (MD) simulations, to study the effects of cholesterol (Chol) and ceramide (Cer) on free volume voids in sphingomyelin (SM) or dipalmitoylphosphatidylcholine (DPPC) bilayers. Binary lipid samples with Chol were studied (DPPC:Chol 60:40, SM:Chol 60:40 mol ratio), and no phase transition was detected in the 20-60 °C range, in agreement with calorimetric data. Chol-driven liquid-ordered phase showed an intermediate free volume void size as compared to gel and fluid phases. For SM and SM:Cer (85:15 mol:mol) model membranes measured in the 20-60 °C range the gel-to-fluid phase transition could be observed with a related increase in free volume, which was more pronounced for the SM:Cer sample. MD simulations suggest a hitherto unsuspected lipid tilting in SM:Cer bilayers but not in pure SM. Ternary samples of DPPC:Cer:Chol (54:23:23) and SM:Cer:Chol (54:23:23) were measured, and a clear pattern of free volume increase was observed in the 20-60 °C because of the gel-to-fluid transition. Interestingly, MD simulations showed a tendency of Cer to change its distribution along the membrane to make room for Chol in ternary mixtures. The results suggest that the gel phase formed in these ternary mixtures is stabilized by Chol-Cer interactions.
authors.affiliation: Biofisika Institute (CSIC, UPV/EHU) , 48080, Bilbao, Spain.|Departamento de Bioquímica, University of the Basque Country (UPV/EHU) , 48080 Bilbao, Spain.
authors.forename: Aritz B
authors.initials: AB
authors.lastname: García-Arribas
authors.affiliation: Department of Electricity and Electronics, University of the Basque Country (UPV/EHU) , 48940 Leioa, Basque Country, Spain.
authors.forename: Eneko
authors.initials: E
authors.lastname: Axpe
authors.affiliation: Kimika Fakultatea, Euskal Herriko Unibertsitatea (UPV/EHU) , 20080 Donostia, Euskadi, Spain.|Donostia International Physics Center (DIPC) , 20018 Donostia, Basque Country, Spain.
authors.forename: Jon Iñaki
authors.initials: JI
authors.lastname: Mujika
authors.affiliation: Department of Electricity and Electronics, University of the Basque Country (UPV/EHU) , 48940 Leioa, Basque Country, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Mérida
authors.affiliation: Biofisika Institute (CSIC, UPV/EHU) , 48080, Bilbao, Spain.|Departamento de Bioquímica, University of the Basque Country (UPV/EHU) , 48080 Bilbao, Spain.
authors.forename: Jon V
authors.initials: JV
authors.lastname: Busto
authors.affiliation: Biofisika Institute (CSIC, UPV/EHU) , 48080, Bilbao, Spain.|Departamento de Bioquímica, University of the Basque Country (UPV/EHU) , 48080 Bilbao, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Sot
authors.affiliation: Biofisika Institute (CSIC, UPV/EHU) , 48080, Bilbao, Spain.|Departamento de Bioquímica, University of the Basque Country (UPV/EHU) , 48080 Bilbao, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Alonso
authors.affiliation: Kimika Fakultatea, Euskal Herriko Unibertsitatea (UPV/EHU) , 20080 Donostia, Euskadi, Spain.|Donostia International Physics Center (DIPC) , 20018 Donostia, Basque Country, Spain.
authors.forename: Xabier
authors.initials: X
authors.lastname: Lopez
authors.affiliation: Department of Applied Physics II, University of the Basque Country (UPV/EHU) , 48940 Leioa, Basque Country, Spain.
authors.forename: Jose Ángel
authors.initials: JÁ
authors.lastname: García
authors.affiliation: Kimika Fakultatea, Euskal Herriko Unibertsitatea (UPV/EHU) , 20080 Donostia, Euskadi, Spain.|Donostia International Physics Center (DIPC) , 20018 Donostia, Basque Country, Spain.
authors.forename: Jesus M
authors.initials: JM
authors.lastname: Ugalde
authors.affiliation: Department of Electricity and Electronics, University of the Basque Country (UPV/EHU) , 48940 Leioa, Basque Country, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Plazaola
authors.affiliation: Biofisika Institute (CSIC, UPV/EHU) , 48080, Bilbao, Spain.|Departamento de Bioquímica, University of the Basque Country (UPV/EHU) , 48080 Bilbao, Spain.
authors.forename: Félix M
authors.initials: FM
authors.lastname: Goñi
mesh_terms: D002518:Ceramides / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D010743:Phospholipids / Q000737:chemistry*; D013057:Spectrum Analysis
chemical_list: D002518:Ceramides; D008051:Lipid Bilayers; D010743:Phospholipids; D002784:Cholesterol