TY - JOUR
T1 - Sphingomyelin Stereoisomers Reveal That Homophilic Interactions Cause Nanodomain Formation
AU - Yano, Yo
AU - Hanashima, Shinya
AU - Yasuda, Tomokazu
AU - Tsuchikawa, Hiroshi
AU - Matsumori, Nobuaki
AU - Kinoshita, Masanao
AU - Al Sazzad, Md Abdullah
AU - Slotte, J. Peter
AU - Murata, Michio
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research (S) 16H06315 and by (C) 15K01801 from Japan Society for the Promotion of Science. Y.Y. was supported by Japan Science and Technology Agency Exploratory Research for Advanced Technology Lipid Active Structure Project. (JPMJER1005). The Slotte laboratory was supported by grants from the Sigrid Juselius Foundation, the Jane and Aatos Erkko Foundation, and the Magnus Ehrnrooth Foundation.
Funding Information:
This work was supported by Grants-in-Aid for Scientific Research (S) 16H06315 and by (C) 15K01801 from Japan Society for the Promotion of Science . Y.Y. was supported by Japan Science and Technology Agency Exploratory Research for Advanced Technology Lipid Active Structure Project. ( JPMJER1005 ). The Slotte laboratory was supported by grants from the Sigrid Juselius Foundation , the Jane and Aatos Erkko Foundation , and the Magnus Ehrnrooth Foundation .
Publisher Copyright:
© 2018 Biophysical Society
PY - 2018/10/16
Y1 - 2018/10/16
N2 - Sphingomyelin is an abundant lipid in some cellular membrane domains, such as lipid rafts. Hydrogen bonding and hydrophobic interactions of the lipid with surrounding components such as neighboring sphingomyelin and cholesterol (Cho) are widely considered to stabilize the raft-like liquid-ordered (Lo) domains in membrane bilayers. However, details of their interactions responsible for the formation of Lo domains remain largely unknown. In this study, the enantiomer of stearoyl sphingomyelin (ent-SSM) was prepared, and its physicochemical properties were compared with the natural SSM and the diastereomer of SSM to examine possible stereoselective lipid-lipid interactions. Interestingly, differential scanning calorimetry experiments demonstrated that palmitoyl sphingomyelin, with natural stereochemistry, exhibited higher miscibility with SSM bilayers than with ent-SSM bilayers, indicating that the homophilic sphingomyelin interactions occurred in a stereoselective manner. Solid-state 2H NMR revealed that Cho elicited its ordering effect very similarly on SSM and ent-SSM (and even on the diastereomer of SSM), suggesting that SSM-Cho interactions are not significantly affected by stereospecific hydrogen bonding. SSM and ent-SSM formed gel-like domains with very similar lateral packing in SSM/Cho/palmitoyloleoyl phosphatidylcholine membranes, as shown by fluorescence lifetime experiments. This observation can be explained by a homophilic hydrogen-bond network, which was largely responsible for the formation of gel-like nanodomains of SSMs (or ent-SSM). Our previous study revealed that Cho-poor gel-like domains contributed significantly to the formation of an Lo phase in sphingomyelin/Cho membranes. The results of the study presented here further show that SSM-SSM interactions occur near the headgroup region, whereas hydrophobic SSM-Cho interactions appeared important in the bilayer interior for Lo domain formation. The homophilic interactions of sphingomyelins could be mainly responsible for the formation of the domains of nanometer size, which may correspond to the small sphingomyelin/Cho-based rafts that temporally occur in biological membranes.
AB - Sphingomyelin is an abundant lipid in some cellular membrane domains, such as lipid rafts. Hydrogen bonding and hydrophobic interactions of the lipid with surrounding components such as neighboring sphingomyelin and cholesterol (Cho) are widely considered to stabilize the raft-like liquid-ordered (Lo) domains in membrane bilayers. However, details of their interactions responsible for the formation of Lo domains remain largely unknown. In this study, the enantiomer of stearoyl sphingomyelin (ent-SSM) was prepared, and its physicochemical properties were compared with the natural SSM and the diastereomer of SSM to examine possible stereoselective lipid-lipid interactions. Interestingly, differential scanning calorimetry experiments demonstrated that palmitoyl sphingomyelin, with natural stereochemistry, exhibited higher miscibility with SSM bilayers than with ent-SSM bilayers, indicating that the homophilic sphingomyelin interactions occurred in a stereoselective manner. Solid-state 2H NMR revealed that Cho elicited its ordering effect very similarly on SSM and ent-SSM (and even on the diastereomer of SSM), suggesting that SSM-Cho interactions are not significantly affected by stereospecific hydrogen bonding. SSM and ent-SSM formed gel-like domains with very similar lateral packing in SSM/Cho/palmitoyloleoyl phosphatidylcholine membranes, as shown by fluorescence lifetime experiments. This observation can be explained by a homophilic hydrogen-bond network, which was largely responsible for the formation of gel-like nanodomains of SSMs (or ent-SSM). Our previous study revealed that Cho-poor gel-like domains contributed significantly to the formation of an Lo phase in sphingomyelin/Cho membranes. The results of the study presented here further show that SSM-SSM interactions occur near the headgroup region, whereas hydrophobic SSM-Cho interactions appeared important in the bilayer interior for Lo domain formation. The homophilic interactions of sphingomyelins could be mainly responsible for the formation of the domains of nanometer size, which may correspond to the small sphingomyelin/Cho-based rafts that temporally occur in biological membranes.
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U2 - 10.1016/j.bpj.2018.08.042
DO - 10.1016/j.bpj.2018.08.042
M3 - Article
C2 - 30274830
AN - SCOPUS:85054004570
VL - 115
SP - 1530
EP - 1540
JO - Biophysical Journal
JF - Biophysical Journal
SN - 0006-3495
IS - 8
ER -