Laurdan and Di-4-ANEPPDHQ Influence the Properties of Lipid Membranes: A Classical Molecular Dynamics and Fluorescence Study

Suhaj, Adam; Gowland, Duncan; Bonini, Nicola; Owen, Dylan M.; Lorenz, Christian D.

doi:10.1021/acs.jpcb.0c09496

Cited by 23 publications

(20 citation statements)

References 75 publications

(106 reference statements)

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“…Experimental techniques, such as deuterium NMR, , can directly measure S CD . The fluorescence spectroscopy using the environment-sensitive probe Laurdan provides the generalized polarization (GP) parameter of the lipids (also called as Laurdan GP order), which measures the local ordering of the lipids around the probe. , It was observed that the Laurdan GP and the deuterium NMR order parameters are in a linear relationship with each other . The MD simulation can directly calculate S CD of the lipid.…”

Section: Resultsmentioning

confidence: 99%

How Do Urea and Trimethylamine N-Oxide Influence the Dehydration-Induced Phase Transition of a Lipid Membrane?

Maiti

Daschakraborty

2021

J. Phys. Chem. B

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Living organisms are often exposed to extreme dehydration, which is detrimental to the structure and function of the cell membrane. The lipid membrane undergoes fluid-to-gel phase transition due to dehydration and thus loses fluidity and functionality. To protect the fluid phase of the bilayer these organisms adopt several strategies. Enhanced production of small polar organic solutes (also called osmolytes) is one such strategy. Urea and trimethylamine N-oxide (TMAO) are two osmolytes found in different organisms combating osmotic stress. Previous experiments have found that both these osmolytes have strong effects on lipid membrane under different hydration conditions. Urea prevents the dehydration-induced phase transition of the lipid membrane by directly interacting with the lipids, while TMAO does not inhibit the phase transition. To provide atomistic insights, we have carried out all-atom molecular dynamics (MD) simulation of a lipid membrane under varying hydration levels and studied the effect of these osmolytes on different structural and dynamic properties of the membrane. This study suggests that urea significantly inhibits the dehydration-induced fluid-to-gel phase transition by strongly interacting with the lipid membrane via hydrogen bonds, which balances the reduced lipid hydration due to the decreasing water content. In contrast, TMAO is excluded from the membrane surface due to unfavorable interaction with the lipids. This induces further dehydration of the lipids which reinforces the fluid-to-gel phase transition. We have also studied the counteractive role of TMAO on the effect of urea on lipid membrane when both the osmolytes are present. TMAO draws some urea molecules out of the membrane and thereby reduces the effect of urea on the lipid membrane at lower hydration levels. This is similar to the counteraction of urea's deleterious ef fects on protein by TMAO. All these observations are consistent with the experimental results and thus provide deep molecular insights into the role of these osmolytes in protecting the fluid phase of the membrane, the key survival strategy against osmotic-stress-induced dehydration.

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Section: Resultsmentioning

confidence: 99%

How Do Urea and Trimethylamine N-Oxide Influence the Dehydration-Induced Phase Transition of a Lipid Membrane?

Maiti

Daschakraborty

2021

J. Phys. Chem. B

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“…Fluorescent labels [514][515][516][517][518][519][520][521][522][523][524][525][526][527][528][529] Fragrance Musk xylene [132] 2-aminoethoxydiphenyl borate (inhibitor of IP 3 receptors and TRP channels) [530] Organic solvents…”

Section: Application Xenobioticmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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“…Fluorescence microscopy with environmentally sensitive probes Dyes change the composition of the bilayers and may alter properties (60). They also do not generally allow the environment around specific molecules to be probed as the dyes are usually untargeted.…”

Section: Methods Limitations Required Developmentsmentioning

confidence: 99%

The Role of Protein and Lipid Clustering in Lymphocyte Activation

et al. 2021

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Lymphocytes must strike a delicate balance between activating in response to signals from potentially pathogenic organisms and avoiding activation from stimuli emanating from the body's own cells. For cells, such as T or B cells, maximizing the efficiency and fidelity, whilst minimizing the crosstalk, of complex signaling pathways is crucial. One way of achieving this control is by carefully orchestrating the spatiotemporal organization of signaling molecules, thereby regulating the rates of protein-protein interactions. This is particularly true at the plasma membrane where proximal signaling events take place and the phenomenon of protein microclustering has been extensively observed and characterized. This review will focus on what is known about the heterogeneous distribution of proteins and lipids at the cell surface, illustrating how such distributions can influence signaling in health and disease. We particularly focus on nanoscale molecular organization, which has recently become accessible for study through advances in microscope technology and analysis methodology.

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Laurdan and Di-4-ANEPPDHQ Influence the Properties of Lipid Membranes: A Classical Molecular Dynamics and Fluorescence Study

Cited by 23 publications

References 75 publications

How Do Urea and Trimethylamine N-Oxide Influence the Dehydration-Induced Phase Transition of a Lipid Membrane?

How Do Urea and Trimethylamine N-Oxide Influence the Dehydration-Induced Phase Transition of a Lipid Membrane?

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

The Role of Protein and Lipid Clustering in Lymphocyte Activation

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