Alteration of lipid membrane structure and dynamics by diacylglycerols with unsaturated chains

Alwarawrah, Mohammad; Hussain, Fazle; Huang, Juyang

doi:10.1016/j.bbamem.2015.11.014

Cited by 29 publications

(40 citation statements)

References 67 publications

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“…4 b ), demonstrating that DAG promotes the ordering of lipid acyl chains. A similar increase of membrane lipid ordering in the presence of DAG was reported ( 15 , 50 ). Cholesterol is also known to be one of the most effective molecules in the cell membranes to cause lipid ordering.…”

Section: Discussionsupporting

confidence: 85%

Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration

Nomura

Yamaguchi

Mori

et al. 2019

Biophysical Journal

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After a nascent chain of a membrane protein emerges from the ribosomal tunnel, the protein is integrated into the cell membrane. This process is controlled by a series of proteinaceous molecular devices, such as signal recognition particles and Sec translocons. In addition to these proteins, we discovered two endogenous components regulating membrane protein integration in the inner membrane of Escherichia coli . The integration is blocked by diacylglycerol (DAG), whereas the blocking is relieved by a glycolipid named membrane protein integrase (MPIase). Here, we investigated the influence of these integration-blocking and integration-promoting factors on the physicochemical properties of membrane lipids via solid-state NMR and fluorescence measurements. These factors did not have destructive effects on membrane morphology because the membrane maintained its lamellar structure and did not fuse in the presence of DAG and/or MPIase at their effective concentrations. We next focused on membrane flexibility. DAG did not affect the mobility of the membrane surface, whereas the sugar chain in MPIase was highly mobile and enhanced the flexibility of membrane lipid headgroups. Comparison with a synthetic MPIase analog revealed the effects of the long sugar chain on membrane properties. The acyl chain order inside the membrane was increased by DAG, whereas the increase was cancelled by the addition of MPIase. MPIase also loosened the membrane lipid packing. Focusing on the transbilayer movement, MPIase reduced the rapid flip-flop motion of DAG. On the other hand, MPIase could not compensate for the diminished lateral diffusion by DAG. These results suggest that by manipulating the membrane lipids dynamics, DAG inhibits the protein from contacting the inner membrane, whereas the flexible long sugar chain of MPIase increases the opportunity for interaction between the membrane and the protein, leading to membrane integration of the newly formed protein.

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Section: Discussionsupporting

confidence: 85%

Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration

Nomura

Yamaguchi

Mori

et al. 2019

Biophysical Journal

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“…Penetration of DAG molecules into PC bilayers has been reported for several lipid mixtures, where it is commonly shown to lead to an increase in bilayer organization and thickness. 9 , 17 , 21 , 32 In MD simulations of 10% DAG and 10% PA systems, we observed no significant change in the overall bilayer thickness (∼39.2 Å) over the course of a 200 ns simulation, although there is 0.3 Å higher fluctuation in the DAG system ( Figure S6 ). This is comparable with SANS experiments, which showed the PC bilayer thickness to be 36 Å at time t = 0 ( Table 1 ).…”

Section: Resultsmentioning

confidence: 88%

“… 20 A recent single-concentration study of the diacylglycerols DPG, POG, and DOG in POPC membrane bilayers reported that this decrease in lateral diffusion of lipids is proportional to the level of DAG unsaturation. 21 …”

Section: Introductionmentioning

confidence: 99%

Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement

et al. 2018

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Understanding the origins of lipid membrane bilayer rearrangement in response to external stimuli is an essential component of cell biology and the bottom-up design of liposomes for biomedical applications. The enzymes phospholipase C and D (PLC and PLD) both cleave the phosphorus–oxygen bonds of phosphate esters in phosphatidylcholine (PC) lipids. The atomic position of this hydrolysis reaction has huge implications for the stability of PC-containing self-assembled structures, such as the cell wall and lipid-based vesicle drug delivery vectors. While PLC converts PC to diacylglycerol (DAG), the interaction of PC with PLD produces phosphatidic acid (PA). Here we present a combination of small-angle scattering data and all-atom molecular dynamics simulations, providing insights into the effects of atomic-scale reorganization on the supramolecular assembly of PC membrane bilayers upon enzyme-mediated incorporation of DAG or PA. We observed that PC liposomes completely disintegrate in the presence of PLC, as conversion of PC to DAG progresses. At lower concentrations, DAG molecules within fluid PC bilayers form hydrogen bonds with backbone carbonyl oxygens in neighboring PC molecules and burrow into the hydrophobic region. This leads initially to membrane thinning followed by a swelling of the lamellar phase with increased DAG. At higher DAG concentrations, localized membrane tension causes a change in lipid phase from lamellar to the hexagonal and micellar cubic phases. Molecular dynamics simulations show that this destabilization is also caused in part by the decreased ability of DAG-containing PC membranes to coordinate sodium ions. Conversely, PLD-treated PC liposomes remain stable up to extremely high conversions to PA. Here, the negatively charged PA headgroup attracts significant amounts of sodium ions from the bulk solution to the membrane surface, leading to a swelling of the coordinated water layer. These findings are a vital step toward a fundamental understanding of the degradation behavior of PC lipid membranes in the presence of these clinically relevant enzymes, and toward the rational design of diagnostic and drug delivery technologies for phospholipase-dysregulation-based diseases.

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“…Other research has shown that DAGs can be highly localised in specific areas of the membrane during cellular growth (29), potentially increasing the damage to the lamellar structure of the membrane. However, low concentrations of DAGs can replace ERG in membrane microdomains (30), making the membrane more rigid (11). Besides the membrane structure itself, it is possible that transformants have a different rate of acetic acid efflux, which could influence the net influx of acetic acid.…”

Section: Storage Lipidsmentioning

confidence: 99%

“…The main protein in the PM is Pma1 (10), and the main sterol is ergosterol (ERG). The latter can reside partly in the interior of the lipid bilayer, increasing membrane rigidity (11). The lipid fraction of the S. cerevisiae PM consists of several of lipids, and a simplified schematic of S. cerevisiae lipid metabolism is shown in Figure 1B.…”

Section: Introductionmentioning

confidence: 99%

Molecular-dynamics-simulation-guided membrane engineering of Saccharomyces cerevisiae by overexpression of plant FAE1 and GPAT5 genes increases fatty acid chain length in membrane lipids

Maertens

Scrima

Lambrughi

et al. 2020

Preprint

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Background The use of lignocellulosic-based fermentation media will be a necessary part of the transition to a circular bio-economy. These media contain many inhibitors to microbial growth, including acetic acid. Under industrially relevant conditions, acetic acid enters the cell predominantly through passive diffusion across the plasma membrane. The lipid composition of the membrane determines the rate of uptake of acetic acid, and thicker, more rigid membranes impede passive diffusion. Results We hypothesized that the elongation of glycerophospholipid fatty acids would lead to thicker and more rigid membranes, reducing the influx of acetic acid. Molecular dynamics simulations were used to predict the changes in membrane properties. Overexpression of Arabidopsis thaliana genes FAE1 and GPAT5 increased the average fatty acid chain length. However, this did not lead to a reduction in the net uptake rate of acetic acid. Conclusions Despite successful strain engineering, the net uptake rate of acetic acid did not decrease. We suggest that changes in the relative abundance of certain membrane lipid headgroups could mitigate the effect of longer fatty acid chains, resulting in a higher net uptake rate of acetic acid.

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Alteration of lipid membrane structure and dynamics by diacylglycerols with unsaturated chains

Cited by 29 publications

References 67 publications

Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration

Alteration of Membrane Physicochemical Properties by Two Factors for Membrane Protein Integration

Fate of Liposomes in the Presence of Phospholipase C and D: From Atomic to Supramolecular Lipid Arrangement

Molecular-dynamics-simulation-guided membrane engineering of Saccharomyces cerevisiae by overexpression of plant FAE1 and GPAT5 genes increases fatty acid chain length in membrane lipids

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