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Structure of Phospholipid Mixed Micelles (Bicelles) Studied by Small-Angle X‑ray Scattering
journal contribution
posted on 2018-11-01, 00:00 authored by Henriette
G. Mortensen, Grethe V. Jensen, Sara K. Hansen, Thomas Vosegaard, Jan Skov PedersenMixed
phospholipid micelles (bicelles) are widely applied in nuclear
magnetic resonance (NMR) studies of membrane proteins in solution,
as they can solubilize these proteins and provide a membrane-like
environment. In this work, the structure of bicelles of dihexanoyl
phosphatidyl choline (DHPC) and dimyristoyl phosphatidyl choline (DMPC)
at different ratios was determined by small-angle X-ray scattering
(SAXS) at 37 °C. Samples with concentrations as applied for NMR
measurements with 28 wt % lipids were diluted to avoid concentration
effects in the SAXS data. The DMPC/DHPC ratio within the bicelles
was kept constant by diluting with solutions of finite DHPC concentrations,
where the concentration of free DHPC is the same as in the original
solution. Absolute-scale modeling of the SAXS data using molecular
and concentration constraints reveals a relatively complex set of
morphologies of the lipid aggregates as a function of the molar ratio Q of DMPC to DHPC. At Q = 0 (pure DHPC
lipids), oblate core–shell micelles are present. At Q = 0.5, the bicelles have a tablet-shaped core–shell
cylindrical form with an ellipsoidal cross section. For Q = 1, 2, 3.2, and 4, the bicelles have a rectangular cuboidal structure
with a core and a shell, for which the overall length and width increase
with Q. At Q = ∞ (pure DMPC),
there is coexistence between multilamellar structures and free bilayers.
For Q = 1–4, the hydrocarbon core is relatively
narrow and the headgroup thickness on the flat areas is larger than
that of, respectively, pure DHPC and DMPC, suggesting some mixing
of DHPC into these areas and staggering of the molecules. This is
further supported by comparisons of the ratio of the areas of rim
and flat parts and estimates of the composition of the flat areas.