High pressure volumetric measurements in dipalmitoylphosphatidylcholine bilayers

Tosh, R; Collings, Peter J.

doi:10.1016/0005-2736(86)90312-3

Cited by 38 publications

(21 citation statements)

References 19 publications

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“…The inclusion of amphipathic peptides at the interface of the bilayer stretches the membrane area that forces the interior of the bilayer-i.e., the hydrocarbon chain region-to become thinner but without breakage. Hydrocarbons have very small volume compressibility (17); therefore, the fractional area increase of a lipid bilayer is closely equal to its fractional thickness decrease. As P/L increases above P/L*, an increasing fraction of melittin helices become perpendicular to the bilayers, and pores are formed.…”

Section: Resultsmentioning

confidence: 99%

Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides

Lee

Hung

Chen

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

251

279

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How antimicrobial peptides form pores in membranes is of interest as a fundamental membrane process. However, the underlying molecular mechanism, which has potential applications in therapeutics, nonviral gene transfer, and drug delivery, has been in dispute. We have resolved this mechanism by observing the time-dependent process of pore formation in individual giant unilamellar vesicles (GUVs) exposed to a melittin solution. An individual GUV first expanded its surface area at constant volume and then suddenly reversed to expanding its volume at constant area. The area expansion, the volume expansion, and the point of reversal all match the results of equilibrium measurements performed on peptide-lipid mixtures. The mechanism includes a negative feedback that makes peptide-induced pores stable with a well defined size, contrary to the suggestion that peptides disintegrate the membrane in a detergent-like manner.antimicrobial peptides ͉ membrane-thinning effect ͉ stable membrane pore ͉ peptide-induced pore ͉ single-membrane experiment M any water-soluble amphipathic peptides spontaneously bind to membranes and form transmembrane pores when the peptide concentrations exceed certain threshold values. Such pore-forming activities are of interest for many reasons. It is the common mode of action used by the ubiquitous antimicrobial peptides (1). A similar mechanism is used by pore-forming proteins, such as the apoptosis regulator Bcl-2-associated X protein (Bax), which activates pore formation in the outer mitochondria membrane to release the apoptotic factor cytochrome c (2). Understanding the relatively simple process of pore formation by small peptides is an important step toward unraveling more complex membranous conformational changes such as membrane fusion (3). Clarifying the pore-forming mechanism will also facilitate its applications, including developing antimicrobial molecules as human therapeutics (1) or smallmolecule agents for nonviral gene transfer and drug delivery. The physical effects caused by the binding of pore-forming peptides to lipid bilayers have been studied by x-ray and neutron diffraction on peptide-lipid mixtures (4-6). The results showed that peptide binding caused membrane thinning and pores appeared only when the thinning reached a critical fraction of the membrane thickness (4-7). However, the equivalent effects have not been demonstrated by kinetic experiments. This is important because pore formation in cell membranes caused by water-soluble peptides typically occurs as a kinetic process. Here, we report the observation of the time behavior of giant unilamellar vesicles (GUVs) exposed to the peptide melittin in solution. The observed time behavior of individual lipid vesicles, although complex, exhibits the physical effects seen in equilibrium experiments, thereby confirming that the mechanism of kinetic pore formation in single membranes is the same as that governing peptide-lipid interactions in the mixtures. It also implies that the same effect is likely to occur in cell membran...

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Section: Resultsmentioning

confidence: 99%

Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides

Lee

Hung

Chen

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

251

279

View full text Add to dashboard Cite

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“…Likewise, the bilayer has a preferred spacing of the lipid molecules in-plane and will resist any changes in this spacing due to external tension [36]. Finally, experiments suggest that the volume per lipid is conserved [37,38] such that changes in bilayer thickness are accompanied by changes in lipid spacing [2,33]. …”

Section: Resultsmentioning

confidence: 99%

“…We note that the bilayer is roughly forty times more resistant to volume change than area change [37,38]; hence if a transmembrane protein locally thins the bilayer, lipids will expand in the area near the protein to conserve volume. Likewise, if the protein locally thickens the bilayer, lipids near the protein will condense (see Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Cooperative Gating and Spatial Organization of Membrane Proteins through Elastic Interactions

et al. 2007

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Biological membranes are elastic media in which the presence of a transmembrane protein leads to local bilayer deformation. The energetics of deformation allow two membrane proteins in close proximity to influence each other's equilibrium conformation via their local deformations, and spatially organize the proteins based on their geometry. We use the mechanosensitive channel of large conductance (MscL) as a case study to examine the implications of bilayer-mediated elastic interactions on protein conformational statistics and clustering. The deformations around MscL cost energy on the order of 10 kBT and extend ∼3 nm from the protein edge, as such elastic forces induce cooperative gating, and we propose experiments to measure these effects. Additionally, since elastic interactions are coupled to protein conformation, we find that conformational changes can severely alter the average separation between two proteins. This has important implications for how conformational changes organize membrane proteins into functional groups within membranes.

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“…The pressure dependence of the melting transition has been investigated before by various authors. 12,13,16,[18][19][20][21]36,37 It has been shown that the shift of the lipid melting transition is linear with the applied hydrostatic pressure in a pressure range up to at least 2 kbar. However, these authors were mainly interested in the shift of the transition point.…”

Section: Discussionmentioning

confidence: 99%

Enthalpy and Volume Changes in Lipid Membranes. I. The Proportionality of Heat and Volume Changes in the Lipid Melting Transition and Its Implication for the Elastic Constants

2001

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Differential scanning calorimetry, pressure calorimetry, and densitometry have been employed to study the relation between volume and enthalpy changes in the melting regime of lipid membranes. We demonstrate a rigid proportional relation between volume expansion coefficient and heat capacity. This result is first shown in densitometric experiments. It implies that calorimetric profiles obey a simple scaling law for the temperature axes in experiments with applied hydrostatic pressure. In a theoretical paper (Heimburg, T. Biochim. Biophys. Acta 1998, 1415, 147-162), we have argued that this relation has far-reaching consequences for the predictiblity of elastic constants from the heat capacity. The proportionality constant between volume and enthalpy changes is found to be independent of the lipid, which has interesting consequences for the calculation of the elastic constants of biological lipid mixtures with unknown composition. We demonstrate this for lung surfactant, which displays a similar relation between volume and enthalpy changes.

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High pressure volumetric measurements in dipalmitoylphosphatidylcholine bilayers

Cited by 38 publications

References 19 publications

Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides

Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides

Cooperative Gating and Spatial Organization of Membrane Proteins through Elastic Interactions

Enthalpy and Volume Changes in Lipid Membranes. I. The Proportionality of Heat and Volume Changes in the Lipid Melting Transition and Its Implication for the Elastic Constants

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