Analytical techniques and methods for study of drug-lipid membrane interactions

2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Hewen Li ◽  
Tao Zhao ◽  
Zhihua Sun
Keyword(s):  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Lipid Membrane ◽  
Drug Research ◽  
Molecular Level ◽  
Analytical Techniques ◽  
Interaction Process ◽  
Lipid Monolayers ◽  
Membrane Interaction ◽  
Modern Analytical

AbstractA better elucidation of molecular mechanisms underlying drug-membrane interaction is of great importance for drug research and development. To date, different biochemical and biophysical methods have been developed to study biological membranes at molecular level. This review focuses on the recent applications and achievements of modern analytical techniques in the study of drug interactions with lipid membranes, including chromatography, spectrometry, calorimetry, and acoustic sensing. The merits and limitations of these techniques were compared and critically discussed. Moreover, various types of biomimetic model membranes including liposomes, lipid monolayers, and supported lipid monolayers/bilayers were described. General mechanisms underlying drug-membrane interaction process were also briefly introduced.

scholarly journals Physical mechanisms of amyloid nucleation on fluid membranes

2020 ◽  
Vol 117 (52) ◽  
pp. 33090-33098
Author(s):  
Johannes Krausser ◽  
Tuomas P. J. Knowles ◽  
Anđela Šarić
Keyword(s):  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Amyloid Fibrils ◽  
Lipid Membrane ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Physical Mechanisms ◽  
Fluid Membranes ◽  
Protein Membrane ◽  
Protein Rich

Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein–membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways—protein-rich and lipid-rich—and quantify how the membrane fluidity and protein–membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterize the rates and the free-energy profile associated with this heterogeneous nucleation process, in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalyzed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context.

A model for the study of the mechanism of a low pH-induced interaction of the virus fusion proteins and cell membranes

1991 ◽  
Vol 11 (3) ◽  
pp. 131-137 ◽  
Author(s):  
S. E. Glushakova ◽  
A. L. Ksenofontov ◽  
N. V. Fedorova ◽  
L. A. Mazhul ◽  
O. N. Ageeva ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lipid Membranes ◽  
Fusion Proteins ◽  
Cell Membranes ◽  
Molecular Mechanisms ◽  
Lipid Membrane ◽  
Specific Activity ◽  
Low Ph ◽  
Structural Reorganization ◽  
First Results

A model is proposed for the study of molecular mechanisms of a low pH-induced interaction of fusion proteins of enveloped viruses and cell membranes. The model consists of large monolamellar liposomes containing ionophore nigericin in their membranes and ectodomains of fusion protein in their inner space. The process of interaction of the protein with the lipid bilayer is triggered by acidification of the liposomal constituents to the pH of fusion with the help of nigericin by adding citric acid to the outer medium. To visualize the protein structural reorganization, the tritium planigraphy was used.Comparison of the values of specific labelling of the proteins and distribution of radioactivity in individual amino acids in control (at neutral pH) and experimental liposome samples (at the pH of fusion) permits to realise the character of protein-membrane interaction. We have obtained the first results in the study of interaction of the bromelain-released soluble ectodomain of the HAXX molecule (BHA)—with the lipid membrane. The observed increase in the protein specific activity and selective increase in the specific activity of hydrophobic amino acids Ile, Phe and Tyr in experimental liposome samples as compared with the controls did not contradict to the conventional concept, that a hydrophobic N-terminus of HA2 subunit of hemagglutinin is responsible for its interaction with lipid membranes.

scholarly journals Membrane interaction and disulphide-bridge formation in the unconventional secretion of Tau

2021 ◽  
Author(s):  
Marianna Hellén ◽  
Arnab Bhattacherjee ◽  
Riikka-Liisa Uronen ◽  
Henri J. Huttunen
Keyword(s):  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Neuronal Degeneration ◽  
Disulphide Bridge ◽  
Membrane Interaction ◽  
Bridge Formation ◽  
Cellular Processes ◽  
Amphipathic Helices ◽  
Unconventional Secretion

Misfolded, pathological Tau protein propagates from cell to cell causing neuronal degeneration in Alzheimer’s disease and other tauopathies. The molecular mechanisms of this process have remained elusive. Unconventional secretion of Tau takes place via several different routes, including direct penetration through the plasma membrane. Here, we show that Tau secretion requires membrane interaction via disulphide bridge formation. Mutating residues that reduce Tau interaction with membranes or formation of disulphide bridges decrease both Tau secretion from cells, and penetration through artificial lipid membranes. Our results demonstrate that Tau is indeed able to penetrate protein-free membranes in a process independent of active cellular processes and that both membrane interaction and disulphide bridge formation are needed for this process. QUARK-based de novo modelling of the second and third microtubule-binding repeat domains, in which the two cysteine residues of 4R isoforms of Tau are located, supports the concept that this region of Tau could form transient amphipathic helices for membrane interaction.

scholarly journals Physical mechanisms of amyloid nucleation on fluid membranes

2019 ◽  
Author(s):  
Johannes Krausser ◽  
Tuomas P. J. Knowles ◽  
Anđela Šarić
Keyword(s):  
Lipid Membranes ◽  
Molecular Mechanisms ◽  
Amyloid Fibrils ◽  
Lipid Membrane ◽  
Coarse Grained ◽  
Coarse Grained Model ◽  
Physical Mechanisms ◽  
Membrane Affinity ◽  
Fluid Membranes ◽  
Protein Membrane

Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein-membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways and quantify how the membrane fluidity and protein-membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterise the rates and the free energy profile associated to this heterogeneous nucleation process in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalysed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context.

scholarly journals Electrochemical Properties of Lipid Membranes Self-Assembled from Bicelles

Membranes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 11
Author(s):  
Damian Dziubak ◽  
Kamil Strzelak ◽  
Slawomir Sek
Keyword(s):  
Electrochemical Properties ◽  
Self Assembly ◽  
Lipid Membranes ◽  
Lipid Membrane ◽  
Membrane Resistance ◽  
Electrochemical Characteristics ◽  
Freeze Thaw ◽  
Lipid Films ◽  
Supported Lipid Membranes

Supported lipid membranes are widely used platforms which serve as simplified models of cell membranes. Among numerous methods used for preparation of planar lipid films, self-assembly of bicelles appears to be promising strategy. Therefore, in this paper we have examined the mechanism of formation and the electrochemical properties of lipid films deposited onto thioglucose-modified gold electrodes from bicellar mixtures. It was found that adsorption of the bicelles occurs by replacement of interfacial water and it leads to formation of a double bilayer structure on the electrode surface. The resulting lipid assembly contains numerous defects and pinholes which affect the permeability of the membrane for ions and water. Significant improvement in morphology and electrochemical characteristics is achieved upon freeze–thaw treatment of the deposited membrane. The lipid assembly is rearranged to single bilayer configuration with locally occurring patches of the second bilayer, and the number of pinholes is substantially decreased. Electrochemical characterization of the lipid membrane after freeze–thaw treatment demonstrated that its permeability for ions and water is significantly reduced, which was manifested by the relatively high value of the membrane resistance.

scholarly journals Interactions of Linear Analogues of Battacin with Negatively Charged Lipid Membranes

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 192
Author(s):  
Kinga Burdach ◽  
Dagmara Tymecka ◽  
Aneta Urban ◽  
Robert Lasek ◽  
Dariusz Bartosik ◽  
...  
Keyword(s):  
Lipid Membranes ◽  
Liquid Crystalline ◽  
Lipid Membrane ◽  
Attenuated Total Reflection ◽  
Gram Positive ◽  
Insertion Depth ◽  
Force Microscopy ◽  
Acyl Chains ◽  
Hydrophobic Portion ◽  
Membrane Fluidization

The increasing resistance of bacteria to available antibiotics has stimulated the search for new antimicrobial compounds with less specific mechanisms of action. These include the ability to disrupt the structure of the cell membrane, which in turn leads to its damage. In this context, amphiphilic lipopeptides belong to the class of the compounds which may fulfill this requirement. In this paper, we describe two linear analogues of battacin with modified acyl chains to tune the balance between the hydrophilic and hydrophobic portion of lipopeptides. We demonstrate that both compounds display antimicrobial activity with the lowest values of minimum inhibitory concentrations found for Gram-positive pathogens. Therefore, their mechanism of action was evaluated on a molecular level using model lipid films mimicking the membrane of Gram-positive bacteria. The surface pressure measurements revealed that both lipopeptides show ability to bind and incorporate into the lipid monolayers, resulting in decreased ordering of lipids and membrane fluidization. Atomic force microscopy (AFM) imaging demonstrated that the exposure of the model bilayers to lipopeptides leads to a transition from the ordered gel phase to disordered liquid crystalline phase. This observation was confirmed by attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) results, which revealed that lipopeptide action causes a substantial increase in the average tilt angle of lipid acyl chains with respect to the surface normal to compensate for lipopeptide insertion into the membrane. Moreover, the peptide moieties in both molecules do not adopt any well-defined secondary structure upon binding with the lipid membrane. It was also observed that a small difference in the structure of a lipophilic chain, altering the balance between hydrophobic and hydrophilic portion of the molecules, results in different insertion depth of the active compounds.

scholarly journals Emerging Data on the Diversity of Molecular Mechanisms Involving C/D snoRNAs

2021 ◽  
Vol 7 (2) ◽  
pp. 30
Author(s):  
Laeya Baldini ◽  
Bruno Charpentier ◽  
Stéphane Labialle
Keyword(s):  
Ribosomal Rna ◽  
Molecular Mechanisms ◽  
Molecular Level ◽  
Accurate Description ◽  
Small Nucleolar Rnas ◽  
Age Of Maturity ◽  
Non Coding Rnas ◽  
And Function ◽  
Nucleolar Rnas

Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we present these pieces of evidence in light of the current comprehension of the molecular mechanisms that control C/D snoRNA expression and function. From this inventory emerges that an accurate description of these activities at a molecular level is required to let the snoRNA field enter in a second age of maturity.

scholarly journals Identification of Biomolecules Involved in the Adaptation to the Environment of Cold-Loving Microorganisms and Metabolic Pathways for Their Production

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1155
Author(s):  
Eva Garcia-Lopez ◽  
Paula Alcazar ◽  
Cristina Cid
Keyword(s):  
Metabolic Pathways ◽  
Extracellular Polymeric Substances ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Analytical Techniques ◽  
Light Protection ◽  
Domains Of Life ◽  
Mechanisms Of Adaptation ◽  
Resistance To Stress ◽  
Function Discovery

Cold-loving microorganisms of all three domains of life have unique and special abilities that allow them to live in harsh environments. They have acquired structural and molecular mechanisms of adaptation to the cold that include the production of anti-freeze proteins, carbohydrate-based extracellular polymeric substances and lipids which serve as cryo- and osmoprotectants by maintaining the fluidity of their membranes. They also produce a wide diversity of pigmented molecules to obtain energy, carry out photosynthesis, increase their resistance to stress and provide them with ultraviolet light protection. Recently developed analytical techniques have been applied as high-throughoutput technologies for function discovery and for reconstructing functional networks in psychrophiles. Among them, omics deserve special mention, such as genomics, transcriptomics, proteomics, glycomics, lipidomics and metabolomics. These techniques have allowed the identification of microorganisms and the study of their biogeochemical activities. They have also made it possible to infer their metabolic capacities and identify the biomolecules that are parts of their structures or that they secrete into the environment, which can be useful in various fields of biotechnology. This Review summarizes current knowledge on psychrophiles as sources of biomolecules and the metabolic pathways for their production. New strategies and next-generation approaches are needed to increase the chances of discovering new biomolecules.

scholarly journals Rethinking SME default prediction: a systematic literature review and future perspectives

2021 ◽  
Author(s):  
Francesco Ciampi ◽  
Alessandro Giannozzi ◽  
Giacomo Marzi ◽  
Edward I. Altman
Keyword(s):  
Literature Review ◽  
Systematic Literature Review ◽  
Global Financial Crisis ◽  
Analytical Techniques ◽  
Future Research ◽  
Finance Management ◽  
Default Prediction ◽  
Emerging Issues ◽  
Medium Enterprise ◽  
Modern Analytical

AbstractOver the last dozen years, the topic of small and medium enterprise (SME) default prediction has developed into a relevant research domain that has grown for important reasons exponentially across multiple disciplines, including finance, management, accounting, and statistics. Motivated by the enormous toll on SMEs caused by the 2007–2009 global financial crisis as well as the recent COVID-19 crisis and the consequent need to develop new SME default predictors, this paper provides a systematic literature review, based on a statistical, bibliometric analysis, of over 100 peer-reviewed articles published on SME default prediction modelling over a 34-year period, 1986 to 2019. We identified, analysed and reviewed five streams of research and suggest a set of future research avenues to help scholars and practitioners address the new challenges and emerging issues in a changing economic environment. The research agenda proposes some new innovative approaches to capture and exploit new data sources using modern analytical techniques, like artificial intelligence, machine learning, and macro-data inputs, with the aim of providing enhanced predictive results.

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