Simulation Study of the Permeability of a Model Lipid Membrane at the Fluid–Solid Phase Transition

Abstract

When a range of lipid bilayers are melted to the disordered fluid phase from the (much less permeable) ordered gel phase, their permeability to a variety of permeants shows a peak at the transition temperature and drops off with increasing temperature, rather than just rising as melting proceeds. To explore this anomalous behavior, a simulated coarse-grained lipid membrane model that exhibits a phase transition upon expansion or compression was studied to determine how the permeation rate of a simple particle depends on the phase composition in the two-phase region and on particle size. The permeation rate and each phase's area fraction and area density could be directly calculated, along with the probability that the permeant would cross in either phase or in interfacial regions. For large permeants and system sizes, conditions could be found where permeability increases upon compression of the bilayer. Permeation was negligible in the gel phase and, in contrast to the predictions of the "leaky interface" hypothesis, was not enriched in interfacial regions. The anomalous effect could instead be attributed to an increase in the area per lipid of fluid-phase domains. This result motivated a model for the decrease in effective permeability barrier through fluid-phase domains arising from a decrease in the length of the gel/fluid interface at the midpoint of a permeation event.

Tocopheryl Succinate-Induced Structural Changes in DPPC Liposomes: DSC and ANS Fluorescence Studies

“…In pure DPPC, the permeation of the ANS shows the biggest ΔFI max value. This is in agreement with the previously published results showing that the highest transfer of ligands through the membrane occurs at T m [ 44 , 45 , 46 ]. This demonstrates that increasing the presence of both tocopherols decreases the ΔFI max of ANS during its transfer to the interior of the bilayer.…”

Permeability of membranes in the liquid ordered and liquid disordered phases

“…The second, M2, is that permeants are completely blocked in the DPPC regions and only transit along the boundary regions between the DPPC clusters. Behavior supporting M2 has been observed in simulations of biphasic bilayers, where enhanced permeability of water, ions, and larger solutes occurs at the interface between the gel and the fluid phases 32–34 . However, the interleaflet space between DPPC- or PSM-rich regions in the L o phase might be accessible to permeants even when the chain regions are not.…”

Coupling of Membrane Nanodomain Formation and Enhanced Electroporation near Phase Transition

“…Different from the narrow temperature interval of the main phase transition of pure lipid bilayers, an increased Na + permeability was reported for a comparably broad temperature interval of ∼10 K. Importantly, unmodified DPPC vesicles were used in these experiments, i.e., the membrane was free of any ion channel, and the permeability could be altered simply by varying the temperature. Several experimental as well as computational studies followed (see, e.g., ( 17 , 18 , 22 , 24 , 25 )) that addressed the permeability anomaly—also valid for water molecules ( 19 ), larger fluorescent dyes ( 21 ), and in mixed membranes ( 23 )—in more detail. For example, currents through model membranes were observed to be quantized at temperatures close to T m with distinct amplitudes ( 18 , 20 , 21 , 22 ), and their lifetimes were similar to those measured in bilayers containing the ion channel gramicidin A ( 18 ).…”