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2014 ; 106
(11
): 2395-407
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Lipopolysaccharide-induced dynamic lipid membrane reorganization: tubules,
perforations, and stacks
#MMPMID24896118
Adams PG
; Lamoureux L
; Swingle KL
; Mukundan H
; Montaņo GA
Biophys J
2014[Jun]; 106
(11
): 2395-407
PMID24896118
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Lipopolysaccharide (LPS) is a unique lipoglycan, with two major physiological
roles: 1), as a major structural component of the outer membrane of Gram-negative
bacteria and 2), as a highly potent mammalian toxin when released from cells into
solution (endotoxin). LPS is an amphiphile that spontaneously inserts into the
outer leaflet of lipid bilayers to bury its hydrophobic lipidic domain, leaving
the hydrophilic polysaccharide chain exposed to the exterior polar solvent.
Divalent cations have long been known to neutralize and stabilize LPS in the
outer membrane, whereas LPS in the presence of monovalent cations forms highly
mobile negatively-charged aggregates. Yet, much of our understanding of LPS and
its interactions with the cell membrane does not take into account its
amphiphilic biochemistry and charge polarization. Herein, we report fluorescence
microscopy and atomic force microscopy analysis of the interaction between LPS
and fluid-phase supported lipid bilayer assemblies (sLBAs), as model membranes.
Depending on cation availability, LPS induces three remarkably different effects
on simple sLBAs. Net-negative LPS-Na(+) leads to the formation of 100-?m-long
flexible lipid tubules from surface-associated lipid vesicles and the
destabilization of the sLBA resulting in micron-size hole formation. Neutral
LPS-Ca(2+) gives rise to 100-?m-wide single- or multilamellar planar sheets of
lipid and LPS formed from surface-associated lipid vesicles. Our findings have
important implications about the physical interactions between LPS and lipids and
demonstrate that sLBAs can be useful platforms to study the interactions of
amphiphilic virulence factors with cell membranes. Additionally, our study
supports the general phenomenon that lipids with highly charged or bulky
headgroups can promote highly curved membrane architectures due to electrostatic
and/or steric repulsions.
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