Experimental and computational studies of the effects of free DHA on a model phosphatidylcholine membrane

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

doi:10.1016/j.chemphyslip.2018.10.003

Cited by 7 publications

(6 citation statements)

References 47 publications

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“…Furthermore, greater amounts of DHAP in the membrane increase the values of D for each lipid type substantially (Figure ), which means that the membrane is becoming more fluid. This result agrees with previous observations that increased unsaturation in the lipid chains, such as DHAP (and other PUFAs), increases the fluidity of model bilayers. ,,,, The fact that we observe an increased fluidity in the complex membranes studied in this manuscript would lend further support to the idea that DHA increases the local fluidity even within biological membranes but it just may not be measurable with current methods …”

Section: Resultssupporting

confidence: 92%

“…Generally, the sn16:0 and sn18:0 chains show increasing S CH values from carbons 2 to 8 due to tighter packing around the membrane interface, before decreasing toward the terminal carbons in the lipid tails where there is greater orientational flexibility nearing the membrane mid-plane (Figure 2). This trend is in agreement with the trend in S CH for the sn16:0 chains of DPPC in a DPPC membrane containing free DHAP, previously studied by Verde et al 59 As for the sn22:6 chains, the numerous dips along the hydrocarbon tail are characteristic of the disordering effect of carbon−carbon double bonds (Figure 2). The S CH profile for the sn22:6 tails within the BH lipids is consistent with those of DHAP-esterified lipids (double-tailed) from the previous works 26,60,61 and shares a similar profile to that of free DHAP (single-tailed) (Figure 2).…”

Section: ■ Results and Discussionsupporting

confidence: 91%

“…This result agrees with previous observations that increased unsaturation in the lipid chains, such as DHAP (and other PUFAs), increases the fluidity of model bilayers. 29,32,33,59,66 The fact that we observe an increased fluidity in the complex membranes studied in this manuscript would lend further support to the idea that DHA increases the local fluidity even within biological membranes but it just may not be measurable with current methods. 67 Flip-flop Rates of DHAP.…”

Section: ■ Results and Discussionsupporting

confidence: 61%

“…Therefore, understanding how DHAP modifies the properties and permeability of a bilayer will add insight into the prevention methods as well as the development of therapeutic remedies to target detriments associated with low-levels of DHAP (dementia, Alzheimer's disease, Parkinson's disease, poor vision, etc.). 59,76 ■ ASSOCIATED CONTENT * sı Supporting Information…”

Section: ■ Conclusionmentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 92%

Section: ■ Results and Discussionsupporting

confidence: 91%

Section: ■ Results and Discussionsupporting

confidence: 61%

Section: ■ Conclusionmentioning

confidence: 99%

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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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“…Oxidization causes the vulnerable double carbon (CC) bonds within the unsaturated lipid-doped liposomal membrane to break, leading to a controllable drug release. − Docosahexaenoic acid (DHA) is an unsaturated fatty acid derived from the omega-3 polyunsaturated fatty acid found in various foods. It has already been proven to have clear benefits for various diseases, including neuronal damage, heart disease, and cancer. , DHA has shown potential in preparing ROS-responsive drug delivery carriers due to its smart sensitivity and good safety profile. − We can reasonably assume that the DHA liposome may have potential in the development of nanocarriers that are activated by ROS generated by radiotherapy.…”

Section: Introductionmentioning

confidence: 99%