On the lipid flip-flop and phase transition coupling

Porcar, Lionel; Gerelli, Yuri

doi:10.1039/d0sm01161d

Cited by 12 publications

(7 citation statements)

References 41 publications

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“…Upon “flip–flop”, the composition of the inner and outer leaflets is mixed, which can be followed by monitoring the amount of −CH 3 (as opposed to −CD 3 ) groups on the surface. ,, The same idea has also been used in neutron reflectometry by Gerelli and co-workers who deposited a H/D labeled bilayer on silica and studied the loss in contrast over time. However, here it was found that interbilayer exchange was rate limiting and lipid “flip–flop” was too fast within the experimental time window. , “Flip–flop” can also be detected by TR-SANS using asymmetric vesicles where one leaflet contains a deuterated lipid . Similar to the KZAC TR-SANS technique, “flip–flop” can then be monitored by the loss in the overall intensity, which in this contrast condition is not sensitive to intervesicular exchange processes.…”

Section: Introductionmentioning

confidence: 76%

“…However, here it was found that interbilayer exchange was rate limiting and lipid "flip−flop" was too fast within the experimental time window. 33,34 "Flip−flop" can also be detected by TR-SANS using asymmetric vesicles where one leaflet contains a deuterated lipid. 10 Similar to the KZAC TR-SANS technique, "flip−flop" can then be monitored by the loss in the overall intensity, which in this contrast condition is not sensitive to intervesicular exchange processes.…”

Section: ■ Introductionmentioning

confidence: 99%

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Molecular Transport and Growth of Lipid Vesicles Exposed to Antimicrobial Peptides

Nielsen

Lund

2021

Langmuir

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It is well-known that lipids constituting the cytoplasmic membrane undergo continuous reorganization to maintain the appropriate composition important for the integrity of the cell. The transport of lipids is controlled by mainly membrane proteins, but also spontaneous lipid transport between leaflets, lipid “flip–flop”, occurs. These processes do not only occur spontaneously under equilibrium, but also promote structural rearrangements, morphological transitions, and growth processes. It has previously been shown that intravesicular lipid “flip–flop” and intervesicular lipid exchange under equilibrium can be deduced indirectly from contrast variation time-resolved small-angle neutron scattering (TR-SANS) where the molecules are “tagged” using hydrogen/deuterium (H/D) substitution. In this work, we show that this technique can be extended to simultaneously detect changes in the growth and the lipid “flip–flop” and exchange rates induced by a peptide additive on lipid vesicles consisting of DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine), d-DMPC (1,2-dimyristoyl-d 54-sn-glycero-3-phosphocholine), DMPG (1,2-dimyristoyl-sn-glycero-3-phospho-(1′-rac-glycerol)), and small amounts of DMPE-PEG (1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]). Changes in the overall size were independently monitored using dynamic light scattering (DLS). We find that the antimicrobial peptide, indolicidin, accelerates lipid transport and additionally induces limited vesicular growth. Moreover, in TR-SANS experiments using partially labeled lipid mixtures to separately study the kinetics of the lipid components, we show that, whereas peptide addition affects both lipids similarly, DMPG exhibits faster kinetics. We find that vesicular growth is mainly associated with peptide-mediated lipid reorganization that only slightly affects the overall exchange kinetics. This is confirmed by a TR-SANS experiment of vesicles preincubated with peptide showing that after pre-equilibration the kinetics are only slightly slower.

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Section: Introductionmentioning

confidence: 76%

Section: ■ Introductionmentioning

confidence: 99%

Molecular Transport and Growth of Lipid Vesicles Exposed to Antimicrobial Peptides

Nielsen

Lund

2021

Langmuir

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“…In DPPC and DMPC vesicles, the values of 122 kJ/mol 8 and 64 kJ/mol 50 have been reported, whereas a lower value of 50 ± 5 kJ/mol was reported from experiments on supported lipid membranes. 51 These values highlight that not only the lipid type but also the employed experimental technique could affect the result. Still, the range of experimental values in lipid-only membranes is in the same ballpark as our value for the protein-containing membrane.…”

Section: Resultsmentioning

confidence: 99%

The Sec61/TRAP Translocon Scrambles Lipids

Javanainen,

Karki,

Tranter

et al. 2023

Preprint

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Cell growth relies on the rapid flip–flop of newly synthesized lipids across the ER membrane. This process is facilitated without the need for ATP by specific membrane proteins—scramblases—a few of which have been very recently identified in the ER. We have previously resolved the structure of the translocon-associated protein (TRAP) bound to the Sec61 translocon in the ER membrane, and found this complex to render the membrane locally thinner. Moreover, Sec61 and TRAP each contain a crevice rich in polar residues that can shield a lipid head group as it traverses the hydrophobic membrane environment. We thus hypothesized that both Sec61 and TRAP act as ER scramblases. Here, we characterized the scrambling activity of Sec61 and TRAP using extensive molecular dynamics simulations. We observed that both Sec61 and TRAP efficiently scramble lipidsviaa credit card mechanism. We analyzed the kinetics and thermodynamics of lipid scrambling and demonstrated that local membrane thinning provides a key contribution to scrambling efficiency. Both proteins appear seemingly selective towards phosphatidylcholine lipids over phosphatidylethanolamine and phosphatidylserine, yet this behavior rather reflects the trends observed for these lipids in a protein-free membrane. The identified scrambling pathway in Sec61 structure is physiologically rarely unoccupied due to its role in protein translocation. Furthermore, we found that the scrambling activity of this pathway might be impeded by the presence of ions at a physiological concentration. However, the trimeric bundle of TRAPβ, TRAPγ, and TRAPδmight provide scrambling activity insensitive to the functional state of the translocon and the solvent conditions.

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“…15 For phospholipids, a wide range of flip-flop rates has been reported, with the typical time scale for one flip-flop varying from minutes to days. 15,[30][31][32][33][34][35][36][37][38] Likewise, the published values for the inverse flip-flop rates of cholesterol and related sterols were observed to vary from seconds 39,40 to milliseconds. 41 One important conclusion from our simulation study is that the stress asymmetry between the two leaflet tensions of a bilayer membrane represent key parameters for the flip-flop rates.…”

Section: Introductionmentioning

confidence: 99%

Large stress asymmetries of lipid bilayers and nanovesicles generate lipid flip-flops and bilayer instabilities

Sreekumari

Lipowsky

2022

Soft Matter

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On the lipid flip-flop and phase transition coupling

Abstract: We measured the lipid flip-flop of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in solid supported lipid bilayers across their main gel to fluid (Lβ→ Lα) phase transition. By performing time and temperature resolved neutron...

Cited by 12 publications

References 41 publications

Molecular Transport and Growth of Lipid Vesicles Exposed to Antimicrobial Peptides

Molecular Transport and Growth of Lipid Vesicles Exposed to Antimicrobial Peptides

The Sec61/TRAP Translocon Scrambles Lipids

Large stress asymmetries of lipid bilayers and nanovesicles generate lipid flip-flops and bilayer instabilities

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