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Membrane Structure and Function

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Physical Chemistry".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 24208

Special Issue Editors


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Guest Editor
Center for Chemistry and Faculty of Pharmacy, University of Coimbra Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal
Interests: physical chemistry of membranes; membrane lateral organization; lipid–protein interaction; lipid–drug interaction; molecular dynamics simulations; fluorescence spectroscopy; Förster resonance energy transfer
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Guest Editor
Center for Chemistry and Chemistry Department, Faculty of Sciences and Technology, University of Coimbra, 3004-535 Coimbra, Portugal
Interests: membrane biophysics; membrane lateral organization; lipid–drug interaction; membrane permeability; pharmacokinetics; P-glycoprotein; isothermal titration calorimetr; fluorescence spectroscopy
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
CALIXAR, Lyon, France
Interests: Membrane protein, solubilization, stabilization, GPCR, Ion channel, Transporter, detergent, Cryo-EM, Structure/ function relationship, antibody discovery, fragment screening, crystallography, Vaccine

Special Issue Information

Dear Colleagues,

Biological membranes are uniquely placed at the interface of a number of fundamental research areas. Regarding biological sciences, first and foremost, they define the limits and mediate the in-and-out transport of ions and small molecules across cells and intracellular organelles. Secondly, many enzymes are located and carry out their functions in membranes. Finally, cell signaling occurs in large part via conformational alterations of protein and/or lipid components of membranes. From a physical approach, biological membranes are interesting as quasi-two-dimensional multicomponent systems; they display complex thermodynamic behaviors, are sensitive to small changes in environmental variables, and they are, moreover, fundamentally out of equilibrium. Smaller membrane systems, such as liposomes, also present high technological value as carriers, including as vehicles for drug and gene delivery.

Among all described processes and applications, knowledge of membrane structure, organization, and dynamics are of paramount importance. Our current models of membranes emphasize lateral and transverse heterogeneity in the distribution of membrane components, which may occur in different length (from nm to µm) and time (from relatively stable to highly transient) scales. Understanding these phenomena and their relation to variables such as lipid and protein composition, ionic strength, pH, temperature, and presence of solutes is often a formidable challenge, which can only be tackled using a multiplicity of experimental and computational approaches.

In this Special Issue, we invite investigators to contribute original research articles and review articles on all aspects of membrane biophysics. Potential topics include but are not limited to:

- Lipid organization, lipid rafts and nanodomains, and lipid phase equilibria;

- Lipid–protein and lipid–peptide interactions;

- Characterization of the thermodynamics and kinetics of interaction of bioactive solutes with biological membranes;

- Membrane model systems;

- Cutting-edge methodologies for the study of membrane structure and dynamics.

Prof. Dr. Luís M.S. Loura
Prof. Dr. Maria João Moreno
Dr. Anass Jawhari
Guest Editors

Manuscript Submission Information

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Keywords

  • lipid polymorphism and phase equilibria
  • lipid rafts
  • membrane permeability
  • membrane organization
  • lipid–protein interaction
  • lipid–drug interaction
  • membrane fusion
  • computational modeling of membranes
  • novel techniques in biophysics

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Published Papers (6 papers)

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Research

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16 pages, 4125 KiB  
Article
Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons
by Virginia Borroni, Constanza Kamerbeek, María F. Pediconi and Francisco J. Barrantes
Molecules 2020, 25(20), 4838; https://doi.org/10.3390/molecules25204838 - 20 Oct 2020
Cited by 11 | Viewed by 2561
Abstract
Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in [...] Read more.
Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01–1 µM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 nAChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein receptor levels as determined by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 µM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium. Full article
(This article belongs to the Special Issue Membrane Structure and Function)
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20 pages, 4580 KiB  
Article
Influence of Membrane Phase on the Optical Properties of DPH
by Silvio Osella, Markéta Paloncýová, Maryam Sahi and Stefan Knippenberg
Molecules 2020, 25(18), 4264; https://doi.org/10.3390/molecules25184264 - 17 Sep 2020
Cited by 7 | Viewed by 3056
Abstract
The fluorescent molecule diphenylhexatriene (DPH) has been often used in combination with fluorescence anisotropy measurements, yet little is known regarding the non-linear optical properties. In the current work, we focus on them and extend the application to fluorescence, while paying attention to the [...] Read more.
The fluorescent molecule diphenylhexatriene (DPH) has been often used in combination with fluorescence anisotropy measurements, yet little is known regarding the non-linear optical properties. In the current work, we focus on them and extend the application to fluorescence, while paying attention to the conformational versatility of DPH when it is embedded in different membrane phases. Extensive hybrid quantum mechanics/molecular mechanics calculations were performed to investigate the influence of the phase- and temperature-dependent lipid environment on the probe. Already, the transition dipole moments and one-photon absorption spectra obtained in the liquid ordered mixture of sphingomyelin (SM)-cholesterol (Chol) (2:1) differ largely from the ones calculated in the liquid disordered DOPC and solid gel DPPC membranes. Throughout the work, the molecular conformation in SM:Chol is found to differ from the other environments. The two-photon absorption spectra and the ones obtained by hyper-Rayleigh scattering depend strongly on the environment. Finally, a stringent comparison of the fluorescence anisotropy decay and the fluorescence lifetime confirm the use of DPH to gain information upon the surrounding lipids and lipid phases. DPH might thus open the possibility to detect and analyze different biological environments based on its absorption and emission properties. Full article
(This article belongs to the Special Issue Membrane Structure and Function)
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15 pages, 522 KiB  
Article
Integral Representation of Electrostatic Interactions inside a Lipid Membrane
by Guilherme Volpe Bossa and Sylvio May
Molecules 2020, 25(17), 3824; https://doi.org/10.3390/molecules25173824 - 22 Aug 2020
Cited by 3 | Viewed by 2634
Abstract
Interactions between charges and dipoles inside a lipid membrane are partially screened. The screening arises both from the polarization of water and from the structure of the electric double layer formed by the salt ions outside the membrane. Assuming that the membrane can [...] Read more.
Interactions between charges and dipoles inside a lipid membrane are partially screened. The screening arises both from the polarization of water and from the structure of the electric double layer formed by the salt ions outside the membrane. Assuming that the membrane can be represented as a dielectric slab of low dielectric constant sandwiched by an aqueous solution containing mobile ions, a theoretical model is developed to quantify the strength of electrostatic interactions inside a lipid membrane that is valid in the linear limit of Poisson-Boltzmann theory. We determine the electrostatic potential produced by a single point charge that resides inside the slab and from that calculate charge-charge and dipole-dipole interactions as a function of separation. Our approach yields integral representations for these interactions that can easily be evaluated numerically for any choice of parameters and be further simplified in limiting cases. Full article
(This article belongs to the Special Issue Membrane Structure and Function)
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Review

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24 pages, 11557 KiB  
Review
Not Just Another Scaffolding Protein Family: The Multifaceted MPPs
by Agnieszka Chytła, Weronika Gajdzik-Nowak, Paulina Olszewska, Agnieszka Biernatowska, Aleksander F. Sikorski and Aleksander Czogalla
Molecules 2020, 25(21), 4954; https://doi.org/10.3390/molecules25214954 - 26 Oct 2020
Cited by 14 | Viewed by 3798
Abstract
Membrane palmitoylated proteins (MPPs) are a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). The ubiquitous expression and multidomain structure of MPPs provide the ability to form diverse protein complexes at the cell membranes, which are involved in [...] Read more.
Membrane palmitoylated proteins (MPPs) are a subfamily of a larger group of multidomain proteins, namely, membrane-associated guanylate kinases (MAGUKs). The ubiquitous expression and multidomain structure of MPPs provide the ability to form diverse protein complexes at the cell membranes, which are involved in a wide range of cellular processes, including establishing the proper cell structure, polarity and cell adhesion. The formation of MPP-dependent complexes in various cell types seems to be based on similar principles, but involves members of different protein groups, such as 4.1-ezrin-radixin-moesin (FERM) domain-containing proteins, polarity proteins or other MAGUKs, showing their multifaceted nature. In this review, we discuss the function of the MPP family in the formation of multiple protein complexes. Notably, we depict their significant role for cell physiology, as the loss of interactions between proteins involved in the complex has a variety of negative consequences. Moreover, based on recent studies concerning the mechanism of membrane raft formation, we shed new light on a possible role played by MPPs in lateral membrane organization. Full article
(This article belongs to the Special Issue Membrane Structure and Function)
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17 pages, 2702 KiB  
Review
Structure and Lateral Organization of Phosphatidylinositol 4,5-bisphosphate
by Luís Borges-Araújo and Fabio Fernandes
Molecules 2020, 25(17), 3885; https://doi.org/10.3390/molecules25173885 - 26 Aug 2020
Cited by 12 | Viewed by 5954
Abstract
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a minor but ubiquitous component of the inner leaflet of the plasma membrane of eukaryotic cells. However, due to its particular complex biophysical properties, it stands out from its neighboring lipids as one of the most important [...] Read more.
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a minor but ubiquitous component of the inner leaflet of the plasma membrane of eukaryotic cells. However, due to its particular complex biophysical properties, it stands out from its neighboring lipids as one of the most important regulators of membrane-associated signaling events. Despite its very low steady-state concentration, PI(4,5)P2 is able to engage in a multitude of simultaneous cellular functions that are temporally and spatially regulated through the presence of localized transient pools of PI(4,5)P2 in the membrane. These pools are crucial for the recruitment, activation, and organization of signaling proteins and consequent regulation of downstream signaling. The present review showcases some of the most important PI(4,5)P2 molecular and biophysical properties as well as their impact on its membrane dynamics, lateral organization, and interactions with other biochemical partners. Full article
(This article belongs to the Special Issue Membrane Structure and Function)
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43 pages, 7339 KiB  
Review
The Secret Lives of Fluorescent Membrane Probes as Revealed by Molecular Dynamics Simulations
by Hugo A. L. Filipe, Maria João Moreno and Luís M. S. Loura
Molecules 2020, 25(15), 3424; https://doi.org/10.3390/molecules25153424 - 28 Jul 2020
Cited by 20 | Viewed by 5443
Abstract
Fluorescent probes have been employed for more than half a century to study the structure and dynamics of model and biological membranes, using spectroscopic and/or microscopic experimental approaches. While their utilization has led to tremendous progress in our knowledge of membrane biophysics and [...] Read more.
Fluorescent probes have been employed for more than half a century to study the structure and dynamics of model and biological membranes, using spectroscopic and/or microscopic experimental approaches. While their utilization has led to tremendous progress in our knowledge of membrane biophysics and physiology, in some respects the behavior of bilayer-inserted membrane probes has long remained inscrutable. The location, orientation and interaction of fluorophores with lipid and/or water molecules are often not well known, and they are crucial for understanding what the probe is actually reporting. Moreover, because the probe is an extraneous inclusion, it may perturb the properties of the host membrane system, altering the very properties it is supposed to measure. For these reasons, the need for independent methodologies to assess the behavior of bilayer-inserted fluorescence probes has been recognized for a long time. Because of recent improvements in computational tools, molecular dynamics (MD) simulations have become a popular means of obtaining this important information. The present review addresses MD studies of all major classes of fluorescent membrane probes, focusing in the period between 2011 and 2020, during which such work has undergone a dramatic surge in both the number of studies and the variety of probes and properties accessed. Full article
(This article belongs to the Special Issue Membrane Structure and Function)
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