Glycerol-Induced Membrane Stiffening: The Role of Viscous Fluid Adlayers

Abstract

Lipid interfaces, ranging from cell membranes to thin surfactant layers that stabilize lung alveoli, are integral to living systems. Such interfaces are often subjected to mechanical forces, and because of their membrane-like geometry, they can easily deform by bending into localized folds. In this work, we explore the role of small molecules (i.e., glycerol) on the mechanical stability of model lung surfactant monolayers. We demonstrate that the presence of glycerol increases local monolayer bending stiffness by orders of magnitude. Our x-ray and neutron reflectivity measurements indicate that water is preferentially depleted, or glycerol is preferentially enriched, at the lipid headgroup/solvent interface, and that this glycerol-enriched layer extends O(10Å) beneath the monolayer with an adsorption free energy of -2.5 to -4.6 kJ/mol. The dramatic change in membrane bending stiffness in the presence of the sugar adlayer is understood in terms of two models: 1), lipid antiplasticization by glycerol; and 2), a continuum mechanical model of the viscous adlayer.

Molecular Dynamics Simulations of Liquid Phase Interfaces: Understanding the Structure of the Glycerol/Water–Dodecane System

“…23 Furthermore, an enrichment of glycerol near the interface has also been observed experimentally for other types of interfaces formed with glycerol/water mixtures (glycerol/water−air 68 and glycerol/water−lipid interfaces). 69 The radial distribution functions shown in Figure 9 further support this interpretation. The dye is located at the interface, the radial distribution function calculated for the interaction with glycerol molecules shows a peak at approximately 5 Å from the dye molecule, whereas the water molecules have their maximum approximately 8 Å from the dye.…”

Glycerol Solvates DPPC Headgroups and Localizes in the Interfacial Regions of Model Pulmonary Interfaces Altering Bilayer Structure

“…The putative stiffening effects of glycerol on gel phase lipid-based models of pulmonary interfaces have been attributed to preferential glycerol localisation at the interfacial region, observed using both X-ray and neutron reflectivity techniques 15 . An increased concentration of headgroup-associated glycerol might be expected to lead to an increase in glycerol-mediated hydrogen bonding in the interfacial region, effectively making lipid bilayers more viscous and thus mechanically stiffer.…”

“…With respect to solvent interactions with the headgroup phosphate, the data from the MD simulations was more enlightening, suggesting that water molecules preferentially locate in the region of the headgroup. This may explain why, even at high glycerol concentrations, some water remains detectably associated with the DPPC headgroup 15 . Overall, the simulations showed that glycerol interacts primarily with the choline moiety of the DPPC headgroup, and that glycerol molecules are able to form associations between neighbouring choline groups, thus effectively cross-linking the lipid headgroups.…”

Permeability of Phospholipid Membrane for Small Polar Molecules Determined from Osmotic Swelling of Giant Phospholipid Vesicles

“…The trend is even more apparent in Figure 8. A possible explanation for the concentration dependence of the apparent membrane permeability is strong evidence for the affinity of polyols to phospholipid headgroups [60,61], which results in the solute concentration adjacent to the membrane being larger than in the bulk solution, which consequently leads to an apparent permeability coefficient which is larger than the actual one. This affinity of polyols to phospholipid headgroups may also account for a large scatter of published data on membrane permeabilities for polyols.…”