Sphingomyelin Stereoisomers Reveal That Homophilic Interactions Cause Nanodomain Formation.

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Yano Y, Hanashima S, Yasuda T, Tsuchikawa H, Matsumori N, Kinoshita M, Al Sazzad MA, Slotte JP, Murata M
Publisher: CELL PRESS
Publication year: 2018
Journal: Biophysical Journal
Journal acronym: Biophys J
Volume number: 115
Issue number: 8
Start page: 1530
End page: 1540
ISSN: 1542-0086


Abstract

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 H-2 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.

Last updated on 2019-09-12 at 02:51