Impact of Acyl Chain Mismatch on the Formation and Properties of Sphingomyelin-Cholesterol Domains

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Nyholm TKM, Engberg O, Hautala V, Tsuchikawa H, Lin K-L, Murata M, Slotte JP
Publisher: Cell Press
Publication year: 2019
Journal: Biophysical Journal
Journal acronym: Biophys J
Volume number: 117
Issue number: 9
Start page: 1577
End page: 1588
ISSN: 1542-0086


Abstract

Lateral segregation and the formation of lateral domains are well-known
phenomena in ternary lipid bilayers composed of an unsaturated (low
gel-to-liquid phase transition temperature (Tm)) phospholipid, a saturated (high-Tm)
phospholipid, and cholesterol. The formation of lateral domains has
been shown to be influenced by differences in phospholipid acyl chain
unsaturation and length. Recently, we also showed that differential
interactions of cholesterol with low- and high-Tm
phospholipids in the bilayer can facilitate phospholipid segregation.
Now, we have investigated phospholipid-cholesterol interactions and
their role in lateral segregation in ternary bilayers composed of
different unsaturated phosphatidylcholines (PCs) with varying acyl chain
lengths, N-palmitoyl-D-erythro-sphingomyelin (PSM),
and cholesterol. Using deuterium NMR spectroscopy, we determined how PSM
was influenced by the acyl chain composition in surrounding PC
environments and correlated this with the affinity of cholestatrienol (a
fluorescent cholesterol analog) for PSM in the different PC
environments. Results from a combination of time-resolved fluorescence
measurements of trans-parinaric acid and Förster resonance
energy transfer experiments showed that the relative affinity of
cholesterol for phospholipids determined the degree to which the sterol
promoted domain formation. From Förster resonance energy transfer,
deuterium NMR, and differential scanning calorimetry results, it was
clear that cholesterol also influenced both the thermostability of the
domains and the degree of order in and outside the PSM-rich domains. The
results of this study have shown that the affinity of cholesterol for
both low-Tm and high-Tm phospholipids and the effects of low- and high-Tm
phospholipids on each other influence both lateral structure and domain
properties in complex bilayers. We envision that similar effects also
contribute to lateral heterogeneity in even more complex biological
membranes.

Last updated on 2020-03-04 at 07:30