A certain proportion of docosahexaenoic acid tends to revert structural and dynamical effects of cholesterol on lipid membranes

Pedroni, Viviana Isabel; Sierra, María Belén; Alarcón, L. M.; Verde, Alejandro R.; Appignanesi, Gustavo A.; Morini, Marcela A.

doi:10.1016/j.bbamem.2021.183584

Cited by 9 publications

(9 citation statements)

References 51 publications

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“…In addition, it is reported that DHA can partially reverse the effect of CHOL on the lipid bilayer, making the membrane more compressible and fluid. 75 Also, in our work, we found that the presence of DHA molecules also had slight effects on the CHOL flip-flop (Figure 7b). Especially, anionic DHA molecules could promote the CHOL flip-flop rate to a certain degree.…”

Section: ■ Model and Methodssupporting

confidence: 64%

Molecular View on the Impact of DHA Molecules on the Physical Properties of a Model Cell Membrane

Zhou

Lin

2022

J. Chem. Inf. Model.

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Docosahexaenoic acid (DHA) is a ω-3 polyunsaturated fatty acid, which can be uptaken by cells and is essential for proper neuronal and retinal function. However, the detailed physical impact of DHA molecules on the plasma membrane is still unclear. Hence, in this work, we carried out μs-scale coarse-grained molecular dynamics (MD) simulations to reveal the interactions between DHA molecules and a model cell membrane. As is known, the cell membrane can segregate into liquid-ordered (L o) and liquid-disordered (L d) membrane domains due to the differential interactions between lipids and proteins. In order to capture this feature, we adopted the three-component phase-separated lipid membranes and considered both anionic and neutral DHA molecules in the current work. Our results showed that DHA molecules can spontaneously self-assemble into nanoclusters, fuse with lipid membranes, and localize preferably in L d membrane domains. During the membrane fusion process, DHA molecules can change the intrinsic transmembrane potential of the lipid membrane, and the effects of anionic DHA molecules are much more significant. Besides, the presence of DHA molecules mainly in the L d membrane domains could regulate the differences in the lipid chain order, membrane thickness, cholesterol preference, and cholesterol flip-flop basically in a concentration-dependent manner, which further promote the stability of the intraleaflet dynamics and inhibit the interleaflet dynamics (or promote membrane domain registration) of the membrane domains. In short, the impact of DHA molecules on the physical properties of a model cell membrane on the molecular level revealed in our work will provide useful insights for understanding the biological functions of DHA molecules.

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Section: ■ Model and Methodssupporting

confidence: 64%

Molecular View on the Impact of DHA Molecules on the Physical Properties of a Model Cell Membrane

Zhou

Lin

2022

J. Chem. Inf. Model.

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“…More recently, Pedroni et al have used a combination of experiments and all-atom molecular dynamics simulations to investigate the effect of free DHA on the structural and dynamic properties of a membrane containing 70% DPPC and 30% cholesterol. They observed that adding 30% DHA to this membrane that the lipid order within the membrane decreases to almost the same order as observed in a pure DPPC membrane, and the diffusion of lipids increases to near the same rate as observed in a pure DPPC membrane …”

Section: Introductionmentioning

confidence: 64%

“…They observed that adding 30% DHA to this membrane that the lipid order within the membrane decreases to almost the same order as observed in a pure DPPC membrane, and the diffusion of lipids increases to near the same rate as observed in a pure DPPC membrane. 40 Free protonated docosahexaenoic acid (DHAP; Figure 1) has recently been shown to modify the lipid composition in flies with Alzheimer's disease, and as a result, it was found to improve their behavioral motor function and increase their lifespan. 41 In this manuscript, we present the results of a series of all-atom molecular dynamics (MD) simulations that were used to investigate how varying concentrations of DHAP affect the structure and dynamics of a complex brain lipid membrane.…”

Section: ■ Introductionmentioning

confidence: 99%

On the Structure and Flip-flop of Free Docosahexaenoic Acid in a Model Human Brain Membrane

Yee

Lorenz

2021

J. Phys. Chem. B

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Among the omega-3 fatty acids, docosahexaenoic acid (DHA, sn22:6) is particularly vital in human brain cell membranes. There is considerable interest in DHA because low-level DHA has been associated with declined cognitive function and poor visual acuity. In this work, atomistic molecular dynamics simulations were used to investigate the effects of free protonated DHA (DHAP) in molar fractions of 0, 17, 30, and 38% in a realistic model of a healthy brain cell membrane comprising 26 lipid types. Numerous flip-flop events of DHAP were observed and categorized as successful or aborted. Novel use of the machine learning technique, density-based spatial clustering of applications with noise (DBSCAN), effectively identified flip-flop events by way of clustering. Our data show that increasing amounts of DHAP in the membrane disorder the bilayer packing, fluidize the membrane, and increase the rates of successful flip-flop from k = 0.2 μs–1 (17% DHAP) to 0.8 μs–1 (30% DHAP) and to 1.3 μs–1 (38% DHAP). In addition, we also provided a detailed understanding of the flip-flop mechanism of DHAP across this complex membrane. Interestingly, we noted the role of hydrogen bonds in two distinct coordinated flip-flop phenomena between two DHAP molecules: double flip-flop and assisted flip-flop. Understanding the effects of various concentrations of DHAP on the dynamics within a lipid membrane and the resulting structural properties of the membrane are important when considering the use of DHAP as a dietary supplement or as a potential therapeutic.

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“…50 The observed effect of the FO on the PC bilayers can be associated mainly with the less ordered arrangement of the hydrocarbon chains of FO triglycerides incorporated into them due to an increase in the total unsaturation of the latter. [49][50][51][52] EOC at the studied concentration contributes a little ( p < 0.05) to the additional disordering of the PC bilayer within the experimental error. 49 This contribution can be explained by the accumulation of lipophilic compounds from EOC in the hydrophobic bilayers of PC liposomes, which disrupts the interactions between the PC acyl chains.…”

Section: Papermentioning

confidence: 91%

“…49,50 This result is consistent with recent research on the effect of LC n-3 PUFA (DHA) on the lipid membrane, making it more compressible and fluid. 51 It is important to note here that the S value of 1.0 is characteristic of rigid lipid bilayers, while a decrease in this value indicates an increase in their fluidity. 50 The observed effect of the FO on the PC bilayers can be associated mainly with the less ordered arrangement of the hydrocarbon chains of FO triglycerides incorporated into them due to an increase in the total unsaturation of the latter.…”

Section: Papermentioning

confidence: 94%

The relationship between the structure and functionality of essential PUFA delivery systems based on sodium caseinate with phosphatidylcholine liposomes without and with a plant antioxidant: an in vitro and in vivo study

et al. 2022

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A certain proportion of docosahexaenoic acid tends to revert structural and dynamical effects of cholesterol on lipid membranes

Cited by 9 publications

References 51 publications

Molecular View on the Impact of DHA Molecules on the Physical Properties of a Model Cell Membrane

Molecular View on the Impact of DHA Molecules on the Physical Properties of a Model Cell Membrane

On the Structure and Flip-flop of Free Docosahexaenoic Acid in a Model Human Brain Membrane

The relationship between the structure and functionality of essential PUFA delivery systems based on sodium caseinate with phosphatidylcholine liposomes without and with a plant antioxidant: an in vitro and in vivo study

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