TY - JOUR
T1 - On the Importance of the C(1)-OH and C(3)-OH Functional Groups of the Long-Chain Base of Ceramide for Interlipid Interaction and Lateral Segregation into Ceramide-Rich Domains
AU - Möuts, Anna
AU - Vattulainen, Elina
AU - Matsufuji, Takaaki
AU - Kinoshita, Masanao
AU - Matsumori, Nobuaki
AU - Slotte, J. Peter
N1 - Funding Information:
*E-mail: jpslotte@abo.fi. ORCID Nobuaki Matsumori: 0000-0003-0495-2044 J. Peter Slotte: 0000-0002-4850-5759 Funding The Slotte laboratory was generously funded by the Sigrid Juselius Foundation, the Jane and Aatos Erkko Foundation, and the Magnus Ehrnrooth Foundation. The Matsumori laboratory was generously funded by the Japan Society for the Promotion of Science Kiban B (15H03121), Grants-in-Aid for Innovative Areas from the Japan Society for the Promotion of Science (26102527 and 16H00773), and the Lipid Active Structure Project, supported by Exploratory Research for Advanced Technology Organization of the Japan Science and Technology Agency. Notes The authors declare no competing financial interest.
Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/12/26
Y1 - 2018/12/26
N2 - Ceramides are important intermediates in sphingolipid biosynthesis (and degradation) and are normally present in only small amounts in unstressed cells. However, following the receptor-mediated activation of neutral sphingomyelinase, sphingomyelin can acutely give rise to substantial amounts of ceramides, which dramatically alter membrane properties. In this study, we have examined the role of the 1-OH and 3-OH functional groups of ceramide for its membrane properties. We have specifically examined how the oxidation of the primary alcohol to COOH or COOMe in palmitoyl ceramide (PCer) or the removal of either the primary alcohol or C(3)-OH (deoxy analogs) affected ceramides' interlipid interactions in fluid phosphatidylcholine bilayers. Measuring the time-resolved fluorescence emission of trans-parinaric acid, or its steady-state anisotropy, we have obtained information about the propensity of the ceramide analogs to form ceramide-rich domains and the thermostability of the formed domains. We observed that the oxidation of the primary alcohol to COOH shifted the ceramide's gel-phase onset concentration to slightly higher values in 1-palmitoyl-2-oleoyl-sn-3-glycero-3-phosphocholine (POPC) bilayers. Methylation of the COOH function of the ceramide did not change the segregation tendency further. The complete removal of the primary alcohol dramatically reduced the ability of 1-deoxy-PCer to form ceramide-rich ordered domains. However, the removal 3-OH (in 3-deoxy-PCer) had only small effects on the lateral segregation of the ceramide analog. The thermostability of the ceramide-rich domains in the POPC bilayers decreased in the following order: 1-OH > COOH > COOMe = 3-deoxy > 1-deoxy. We conclude that ceramide needs a hydrogen-bonding-competent functional group in the C(1) position to be able to form laterally segregated ceramide-rich domains of high packing density in POPC bilayers. The presence or absence of 3-OH was not functionally critical for ceramide's lateral segregation properties.
AB - Ceramides are important intermediates in sphingolipid biosynthesis (and degradation) and are normally present in only small amounts in unstressed cells. However, following the receptor-mediated activation of neutral sphingomyelinase, sphingomyelin can acutely give rise to substantial amounts of ceramides, which dramatically alter membrane properties. In this study, we have examined the role of the 1-OH and 3-OH functional groups of ceramide for its membrane properties. We have specifically examined how the oxidation of the primary alcohol to COOH or COOMe in palmitoyl ceramide (PCer) or the removal of either the primary alcohol or C(3)-OH (deoxy analogs) affected ceramides' interlipid interactions in fluid phosphatidylcholine bilayers. Measuring the time-resolved fluorescence emission of trans-parinaric acid, or its steady-state anisotropy, we have obtained information about the propensity of the ceramide analogs to form ceramide-rich domains and the thermostability of the formed domains. We observed that the oxidation of the primary alcohol to COOH shifted the ceramide's gel-phase onset concentration to slightly higher values in 1-palmitoyl-2-oleoyl-sn-3-glycero-3-phosphocholine (POPC) bilayers. Methylation of the COOH function of the ceramide did not change the segregation tendency further. The complete removal of the primary alcohol dramatically reduced the ability of 1-deoxy-PCer to form ceramide-rich ordered domains. However, the removal 3-OH (in 3-deoxy-PCer) had only small effects on the lateral segregation of the ceramide analog. The thermostability of the ceramide-rich domains in the POPC bilayers decreased in the following order: 1-OH > COOH > COOMe = 3-deoxy > 1-deoxy. We conclude that ceramide needs a hydrogen-bonding-competent functional group in the C(1) position to be able to form laterally segregated ceramide-rich domains of high packing density in POPC bilayers. The presence or absence of 3-OH was not functionally critical for ceramide's lateral segregation properties.
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U2 - 10.1021/acs.langmuir.8b03237
DO - 10.1021/acs.langmuir.8b03237
M3 - Article
C2 - 30507134
AN - SCOPUS:85058803700
SN - 0743-7463
VL - 34
SP - 15864
EP - 15870
JO - Langmuir
JF - Langmuir
IS - 51
ER -