Interaction of Aspirin (Acetylsalicylic Acid) with Lipid Membranes

Barrett, Matthew A.; Zheng, Songbo; Roshankar, Golnaz; Alsop, Richard J.; Belanger, R.; Huynh, Chris; Kučerka, Norbert; Rheinstädter, Maikel C.

doi:10.1371/journal.pone.0034357

Cited by 61 publications

(123 citation statements)

References 17 publications

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“…A series of evenly spaced Bragg peaks was observed from both membranes, indicating well ordered membrane stacks. The lamellar spacings for the membranes complexes without and with the peptide were determined to be 53.6 and 55 Å, respectively, in agreement with previous reports (33)(34)(35)(36).…”

Section: Patch Clamp Recordings From Hek293 Cells Confirm Biophysicalsupporting

confidence: 90%

“…9B. The membrane electron density, (z), is approximated by a one-dimensional Fourier analysis (35,48) where N is the highest order of the Bragg peaks observed in the experiment. The integrated peak intensities, I n , are multiplied by q n to generate the form factors, F(q n ).…”

Section: Methodsmentioning

confidence: 99%

“…The phase problem of crystallography therefore simplifies to the sign problem F(q z ) ϭ Ϯ ͉F(q z )͉, and the phases, n , can only take the values Ϯ1. To deter-mine the phases for this study, a fitting procedure was used, as described previously (33)(34)(35). The calculated electron densities, (z), which are initially on an arbitrary scale, were vertically shifted to fulfill the condition (0) ϭ 0.22 e Ϫ /Å 3 (the electron density of a CH 3 group) in the center of the bilayer.…”

Section: Methodsmentioning

confidence: 99%

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A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC)

Schmidt

Löhrer

Alsop

et al. 2016

Journal of Biological Chemistry

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Edited by George CarmanThe bile acid-sensitive ion channel (BASIC) is a member of the degenerin/epithelial Na ؉ channel (Deg/ENaC) family of ion channels. It is mainly found in bile duct epithelial cells, the intestinal tract, and the cerebellum and is activated by alterations of its membrane environment. Bile acids, one class of putative physiological activators, exert their effect by changing membrane properties, leading to an opening of the channel. The physiological function of BASIC, however, is unknown. Deg/ ENaC channels are characterized by a trimeric subunit composition. Each subunit is composed of two transmembrane segments, which are linked by a large extracellular domain. The termini of the channels protrude into the cytosol. Many Deg/ ENaC channels contain regulatory domains and sequence motifs within their cytosolic domains. In this study, we show that BASIC contains an amphiphilic ␣-helical structure within its N-terminal domain. This ␣-helix binds to the cytosolic face of the plasma membrane and stabilizes a closed state. Truncation of this domain renders the channel hyperactive. Collectively, we identify a cytoplasmic domain, unique to BASIC, that controls channel activity via membrane interaction.

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Section: Patch Clamp Recordings From Hek293 Cells Confirm Biophysicalsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC)

Schmidt

Löhrer

Alsop

et al. 2016

Journal of Biological Chemistry

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“…The electron rich head group can be identified by the absolute maximum in the electron density profile at |z| ~ 22 Å. ρ monotonically decreases towards the bilayer center at z = 0, where CH 3 groups typically reside, with a low electron density. The electron density profile of the d z lo = 59.2 Å domain (blue curve) agrees well with a lipid bilayer with lipids in a well ordered, gel-like state with their lipid chains in an all-trans configuration 14,15 . Together with the information 1.…”

supporting

confidence: 59%

“…The out-of-plane structure of the membrane was determined using specular reflectivity. The relative electron density, ρ(z), is approximated by a 1-dimensional Fourier analysis 15,81 :…”

Section: Preparation Of Ghosts the Preparation Of Rbc Ghosts Was Firmentioning

confidence: 99%

The Molecular Structure of Human Red Blood Cell Membranes From Highly Oriented, Solid Supported Multi-Lamellar Membranes

Himbert

Alsop

Rheinstädter

2018

Biophysical Journal

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We prepared highly oriented, multi-lamellar stacks of human red blood cell (RBC) membranes applied on silicon wafers. RBC ghosts were prepared by hemolysis and applied onto functionalized silicon chips and annealed into multi-lamellar RBC membranes. High resolution X-ray diffraction was used to determine the molecular structure of the stacked membranes. We present direct experimental evidence that these RBC membranes consist of nanometer sized domains of integral coiled-coil peptides, as well as liquid ordered (l o ) and liquid disordered (l d ) lipids. Lamellar spacings, membrane and hydration water layer thicknesses, areas per lipid tail and domain sizes were determined. The common drug aspirin was added to the RBC membranes and found to interact with RBC membranes and preferably partition in the head group region of the l o domain leading to a fluidification of the membranes, i.e., a thinning of the bilayers and an increase in lipid tail spacing. Our results further support current models of RBC membranes as patchy structures and provide unprecedented structural details of the molecular organization in the different domains.The presence of pale cells with no internal content in a blood smear is typically indicative of a disease. These cells are produced by hemolysis and have been named red blood cell (RBC) ghosts based on their appearance under the microscope. RBC ghosts can be prepared artificially [1][2][3] . The first published protocol in 1963 by Dodge, Mitchell and Hanahan describes the extraction of the cell membrane from RBCs through hemolysis and was an essential step in the development of membrane proteomics and lipidomics 4,5 . While there is detailed knowledge of the composition of RBC membranes, information about the molecular organization of these components in the actual membranes is scarce 6 . This is, in particular, a consequence of the lack of suitable experimental techniques. The disordered, patchy and highly dynamic state of biological materials impedes, for instance, the use of high-resolution diffraction techniques as in protein crystallography. To overcome this constraint, we prepared highly oriented stacks of RBC membranes on silicon wafers and studied their molecular properties in-vitro using high resolution X-ray diffraction. The results present evidence for nanometer-sized domains of coiled-coils peptides, as well as liquid ordered (l o ) and liquid disordered (l d ) lipid patches, and give a detailed picture of the molecular organization in these domains.When present in the body, aspirin (acetylsalicylic acid, ASA) and its metabolites interact with the cyclo-oxygenase (COX) pathway. The inhibition of both COX isoforms, COX-1 and COX-2, by higher dose aspirin is believed to lead to analgesic and anti-inflammatory effects, while lower doses, sufficient to inhibit COX-1 activity, lead to anti-platelet activity 7,8 . There is recent evidence that membrane composition and fluidity play an important role in platelet cell function [9][10][11] , possibly related to the formation of rafts 12 .

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Molecular Dynamics Simulation of Small Molecules Interacting with Biological Membranes

et al. 2020

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Cell membranes protect and compartmentalise cells and their organelles. The semi-permeable nature of these membranes controls the exchange of solutes across their structure. Characterising the interaction of small molecules with biological membranes is critical to understanding of physiological processes, drug action and permeation, and many biotechnological applications. This review provides an overview of how molecular simulations are used to study the interaction of small molecules with biological membranes, with a particular focus on the interactions of water, organic compounds, drugs and short peptides with models of plasma cell membrane and stratum corneum lipid bilayers. This review will not delve on other type of membranes which might have different composition and arrangement, such as thylakoid or mitochondrial membranes. The application of unbiased molecular dynamics simulations and enhanced sampling methods such as umbrella sampling, metadynamics and replica exchange are described using key examples. This review demonstrates how state-of-the-art molecular simulations have been used successfully to describe the mechanism of binding and permeation of small molecules with biological membranes, as well as associated changes to the structure and dynamics of these membranes. The review concludes with an outlook on future directions in this field.

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Interaction of Aspirin (Acetylsalicylic Acid) with Lipid Membranes

Cited by 61 publications

References 17 publications

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC)

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC)

The Molecular Structure of Human Red Blood Cell Membranes From Highly Oriented, Solid Supported Multi-Lamellar Membranes

Molecular Dynamics Simulation of Small Molecules Interacting with Biological Membranes

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