Recent Studies on the Behaviour of Lipid Membranes

A special issue of Membranes (ISSN 2077-0375). This special issue belongs to the section "Biological Membrane Composition and Structures".

Deadline for manuscript submissions: closed (20 June 2023) | Viewed by 16093

Special Issue Editors


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Guest Editor
Department of Pharmacy, University of Salerno, 84084 Fisciano, SA, Italy
Interests: antimicrobials; molecular modelling; membranes; biomaterials
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Chemistry and Biology, University of Salerno, 84084 Fisciano, SA, Italy
Interests: vesicles; kinetic modelling; fluorescence; polymers

Special Issue Information

Dear Colleagues,

The construction of artificial models that resemble biological membranes in form and functions is a rapidly growing area of research.  Lipids are the main components of biological membranes; however, cell membranes exhibit a complex composition of lipids and proteins to perform the functions essential for life, such as transport, energy harvesting and signalling. This complexity makes challenging the interpretation of the physicochemical properties ruling these processes. To overcome this, simplified model membrane systems are valid platforms to unveil the nature of the interactions of biological membranes.

The most prominent model membrane systems are liposomes (mainly giant and large vesicles that can be easily monitored through microscopy techniques), monolayers and solid supported bilayers. All these systems allow mimicking of the properties of cell membranes, such as lipid composition, lipid curvature, domains, and rafts.

This Special Issue aims to collect experimental and theoretical investigations on the interactions between model lipid membranes and different kinds of molecules.

For this Special Issue of Membranes, authors are invited to present their recent results, and both original papers and reviews are welcome.

Research areas may include (but are not limited to) the characterization and the dynamical behaviour of lipid membranes with drugs, proteins, fatty acids, polymers, fluorescent probes, and nanoparticles. The interactions can also be predicted theoretically with molecular dynamic (MD) simulations.

We look forward to receiving your contributions.

Dr. Lucia Sessa
Dr. Ylenia Miele
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Membranes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • GUVs, LUVs
  • monolayers
  • self-assembled structures
  • functionalized lipid membranes
  • Molecular dynamics (MD) simulations
  • membrane modelling and composition
  • membrane probes
  • lipid interactions
  • lipid behaviour
  • protein/lipid interactions

Published Papers (8 papers)

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Research

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14 pages, 3254 KiB  
Article
Membrane Order Effect on the Photoresponse of an Organic Transducer
by Vito Vurro, Matteo Moschetta, Gaia Bondelli, Samim Sardar, Arianna Magni, Valentina Sesti, Giuseppe Maria Paternò, Chiara Bertarelli, Cosimo D’Andrea and Guglielmo Lanzani
Membranes 2023, 13(5), 538; https://doi.org/10.3390/membranes13050538 - 22 May 2023
Cited by 2 | Viewed by 1328
Abstract
Non-genetic photostimulation, which allows for control over cellular activity via the use of cell-targeting phototransducers, is widely used nowadays to study and modulate/restore biological functions. This approach relies on non-covalent interactions between the phototransducer and the cell membrane, thus implying that cell conditions [...] Read more.
Non-genetic photostimulation, which allows for control over cellular activity via the use of cell-targeting phototransducers, is widely used nowadays to study and modulate/restore biological functions. This approach relies on non-covalent interactions between the phototransducer and the cell membrane, thus implying that cell conditions and membrane status can dictate the effectiveness of the method. For instance, although immortalized cell lines are traditionally used in photostimulation experiments, it has been demonstrated that the number of passages they undergo is correlated to the worsening of cell conditions. In principle, this could impact cell responsivity against exogenous stressors, including photostimulation. However, these aspects have usually been neglected in previous experiments. In this work, we investigated whether cell passages could affect membrane properties (such as polarity and fluidity). We applied optical spectroscopy and electrophysiological measurements in two different biological models: (i) an epithelial immortalized cell line (HEK-293T cells) and (ii) liposomes. Different numbers of cell passages were compared to a different morphology in the liposome membrane. We demonstrated that cell membranes show a significant decrease in ordered domains upon increasing the passage number. Furthermore, we observed that cell responsivity against external stressors is markedly different between aged and non-aged cells. Firstly, we noted that the thermal-disordering effect that is usually observed in membranes is more evident in aged cells than in non-aged ones. We then set up a photostimulation experiment by using a membrane-targeted azobenzene as a phototransducer (Ziapin2). As an example of a functional consequence of such a condition, we showed that the rate of isomerization of an intramembrane molecular transducer is significantly impaired in aged cells. The reduction in the photoisomerization rate translates in cells with a sustained reduction of the Ziapin2-related hyperpolarization of the membrane potential and an overall increase in the molecule fluorescence. Overall, our results suggest that membrane stimulation strongly depends on membrane order, highlighting the importance of cell passage during the characterization of the stimulation tools. This study can shine light on the correlation between aging and the development of diseases driven by membrane degradation as well as on the different cell responsivities against external stressors, such as temperature and photostimulation. Full article
(This article belongs to the Special Issue Recent Studies on the Behaviour of Lipid Membranes)
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9 pages, 1528 KiB  
Article
Molecular Rearrangements in Protomembrane Models Probed by Laurdan Fluorescence
by Loreto Misuraca, Roland Winter, Bruno Demé, Philippe M. Oger and Judith Peters
Membranes 2023, 13(4), 386; https://doi.org/10.3390/membranes13040386 - 28 Mar 2023
Viewed by 1181
Abstract
Lipid membranes are a key component of living systems and have been essential to the origin of life. One hypothesis for the origin of life assumes the existence of protomembranes with ancient lipids formed by Fischer–Tropsch synthesis. We determined the mesophase structure and [...] Read more.
Lipid membranes are a key component of living systems and have been essential to the origin of life. One hypothesis for the origin of life assumes the existence of protomembranes with ancient lipids formed by Fischer–Tropsch synthesis. We determined the mesophase structure and fluidity of a prototypical decanoic (capric) acid-based system, a fatty acid with a chain length of 10 carbons, and a lipid system consisting of a 1:1 mixture of capric acid with a fatty alcohol of equal chain length (C10 mix). To shed light on the mesophase behavior and fluidity of these prebiotic model membranes, we employed Laurdan fluorescence spectroscopy, which reports on the lipid packing and fluidity of membranes, supplemented by small-angle neutron diffraction data. The data are compared with data of the corresponding phospholipid bilayer systems of the same chain length, 1,2-didecanoyl-sn-glycero-3-phosphocholine (DLPC). We demonstrate that the prebiotic model membranes capric acid and the C10 mix show formation of stable vesicular structures needed for cellular compartmentalization at low temperatures only, typically below 20 °C. They reveal the fluid-like lipid dynamic properties needed for optimal physiological function. High temperatures lead to the destabilization of the lipid vesicles and the formation of micellar structures. Full article
(This article belongs to the Special Issue Recent Studies on the Behaviour of Lipid Membranes)
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8 pages, 1717 KiB  
Communication
A Note on Vestigial Osmotic Pressure
by Hao Wu, Zhong-Can Ou-Yang and Rudolf Podgornik
Membranes 2023, 13(3), 332; https://doi.org/10.3390/membranes13030332 - 14 Mar 2023
Viewed by 1042
Abstract
Recent experiments have indicated that at least a part of the osmotic pressure across the giant unilamellar vesicle (GUV) membrane was balanced by the rapid formation of the monodisperse daughter vesicles inside the GUVs through an endocytosis-like process. Therefore, we investigated a possible [...] Read more.
Recent experiments have indicated that at least a part of the osmotic pressure across the giant unilamellar vesicle (GUV) membrane was balanced by the rapid formation of the monodisperse daughter vesicles inside the GUVs through an endocytosis-like process. Therefore, we investigated a possible osmotic role played by these daughter vesicles for the maintenance of osmotic regulation in the GUVs and, by extension, in living cells. We highlighted a mechanism whereby the daughter vesicles acted as osmotically active solutes (osmoticants), contributing an extra vestigial osmotic pressure component across the membrane of the parent vesicle, and we showed that the consequences were consistent with experimental observations. Our results highlight the significance of osmotic regulation in cellular processes, such as fission/fusion, endocytosis, and exocytosis. Full article
(This article belongs to the Special Issue Recent Studies on the Behaviour of Lipid Membranes)
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18 pages, 3110 KiB  
Article
Super-Resolution Imaging of Plant Receptor-Like Kinases Uncovers Their Colocalization and Coordination with Nanometer Resolution
by Jeremiah Traeger, Dehong Hu, Mengran Yang, Gary Stacey and Galya Orr
Membranes 2023, 13(2), 142; https://doi.org/10.3390/membranes13020142 - 21 Jan 2023
Viewed by 2419
Abstract
Plant cell signaling often relies on the cellular organization of receptor-like kinases (RLKs) within membrane nanodomains to enhance signaling specificity and efficiency. Thus, nanometer-scale quantitative analysis of spatial organizations of RLKs could provide new understanding of mechanisms underlying plant responses to environmental stress. [...] Read more.
Plant cell signaling often relies on the cellular organization of receptor-like kinases (RLKs) within membrane nanodomains to enhance signaling specificity and efficiency. Thus, nanometer-scale quantitative analysis of spatial organizations of RLKs could provide new understanding of mechanisms underlying plant responses to environmental stress. Here, we used stochastic optical reconstruction fluorescence microscopy (STORM) to quantify the colocalization of the flagellin-sensitive-2 (FLS2) receptor and the nanodomain marker, remorin, within Arabidopsis thaliana root hair cells. We found that recovery of FLS2 and remorin in the plasma membrane, following ligand-induced internalization by bacterial-flagellin-peptide (flg22), reached ~85% of their original membrane density after ~90 min. The pairs colocalized at the membrane at greater frequencies, compared with simulated randomly distributed pairs, except for directly after recovery, suggesting initial uncoordinated recovery followed by remorin and FLS2 pairing in the membrane. The purinergic receptor, P2K1, colocalized with remorin at similar frequencies as FLS2, while FLS2 and P2K1 colocalization occurred at significantly lower frequencies, suggesting that these RLKs mostly occupy distinct nanodomains. The chitin elicitor receptor, CERK1, colocalized with FLS2 and remorin at much lower frequencies, suggesting little coordination between CERK1 and FLS2. These findings emphasize STORM’s capacity to observe distinct nanodomains and degrees of coordination between plant cell receptors, and their respective immune pathways. Full article
(This article belongs to the Special Issue Recent Studies on the Behaviour of Lipid Membranes)
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18 pages, 4017 KiB  
Article
Phosphatidylcholine Liposomes Reprogram Macrophages toward an Inflammatory Phenotype
by David M. Cauvi, Dennis Hawisher, Julia Derunes and Antonio De Maio
Membranes 2023, 13(2), 141; https://doi.org/10.3390/membranes13020141 - 21 Jan 2023
Cited by 2 | Viewed by 2168
Abstract
Phospholipids are the major components of cellular membranes and cell-derived vesicles such as exosomes. They are also key components of artificial lipid nanoparticles, allowing the encapsulation and transport of various biological or chemical cargos. Both artificial and natural vesicles could be captured by [...] Read more.
Phospholipids are the major components of cellular membranes and cell-derived vesicles such as exosomes. They are also key components of artificial lipid nanoparticles, allowing the encapsulation and transport of various biological or chemical cargos. Both artificial and natural vesicles could be captured by cells delivering important information that could modulate cellular functions. However, the potential contribution of phospholipids within vesicles altering cellular physiology has been largely underestimated. Here, we showed that macrophages exposed to liposomes made exclusively with palmitoyl oleoyl phosphatidylcholine (POPC) in vivo resulted in a dramatic alteration of the transcriptome profile. Differential gene expression analysis indicated that the exposure to POPC liposomes resulted in a change in the expression of 1598 genes. Moreover, 146 genes were upregulated, and 69 genes were downregulated by incubation with POPC liposomes in contrast to palmitoyl oleoyl phosphatidylserine (POPS) exposure. Signaling pathway impact analysis revealed that 24 signaling pathways were significantly modulated after exposure to POPC liposomes, including the activation of the NF-κB pathway. Indeed, the expression of several cytokines (TNF-α, IL-6, and IL-10) and chemokines (Cxcl1 and Cxcl2) were increased. These observations were validated by the exposure of macrophages to POPC liposomes in culture conditions. In addition, the proteomic analysis of peritoneal cells exposed to POPC liposomes performed by mass spectrometry revealed that the expression of 107 proteins was downregulated after POPC exposure, whereas the expression of 12 proteins was significantly upregulated by this treatment, including seven proteins involved in the neutrophil degranulation pathway. This observation was confirmed by flow cytometry analysis showing the rapid recruitment of neutrophils into the peritoneal cavity after POPC exposure. Overall, these findings demonstrate that the presence of phospholipids within artificial and natural vesicles could be responsible for changes in the function of target cells. Full article
(This article belongs to the Special Issue Recent Studies on the Behaviour of Lipid Membranes)
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13 pages, 2914 KiB  
Article
The Interaction of Anthracycline Based Quinone-Chelators with Model Lipid Membranes: 1H NMR and MD Study
by Olga Yu. Selyutina, Anna V. Mastova and Nikolay E. Polyakov
Membranes 2023, 13(1), 61; https://doi.org/10.3390/membranes13010061 - 3 Jan 2023
Cited by 5 | Viewed by 1573
Abstract
Anthracycline antibiotics, e.g., doxorubicin, daunomycin, and other anthraquinones, are an important family of antitumor agents widely used in chemotherapy, which is currently the principal method for treating many malignancies. Thus, development of improved antitumor drugs with enhanced efficacy remains a high priority. Interaction [...] Read more.
Anthracycline antibiotics, e.g., doxorubicin, daunomycin, and other anthraquinones, are an important family of antitumor agents widely used in chemotherapy, which is currently the principal method for treating many malignancies. Thus, development of improved antitumor drugs with enhanced efficacy remains a high priority. Interaction of anthraquinone-based anticancer drugs with cell membranes attracts significant attention due to its importance in the eventual overcoming of multidrug resistance (MDR). The use of drugs able to accumulate in the cell membrane is one of the possible ways of overcoming MDR. In the present work, the aspects of interaction of anthraquinone 2-phenyl-4-(butylamino)naphtho[2,3-h]quinoline-7,12-dione) (Q1) with a model membrane were studied by means of NMR and molecular dynamics simulations. A fundamental shortcoming of anthracycline antibiotics is their high cardiotoxicity caused by reactive oxygen species (ROS). The important feature of Q1 is its ability to chelate transition metal ions responsible for ROS generation in vivo. In the present study, we have shown that Q1 and its chelating complexes penetrated into the lipid membrane and were located in the hydrophobic part of the bilayer near the bilayer surface. The chelate complex formation of Q1 with metal ions increased its penetration ability. In addition, it was found that the interaction of Q1 with lipid molecules could influence lipid mobility in the bilayer. The obtained results have an impact on the understanding of molecular mechanisms of Q1 biological activity. Full article
(This article belongs to the Special Issue Recent Studies on the Behaviour of Lipid Membranes)
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Review

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16 pages, 6109 KiB  
Review
Phospholipases and Membrane Curvature: What Is Happening at the Surface?
by María Laura Fanani and Ernesto Esteban Ambroggio
Membranes 2023, 13(2), 190; https://doi.org/10.3390/membranes13020190 - 3 Feb 2023
Cited by 3 | Viewed by 2119
Abstract
In this revision work, we emphasize the close relationship between the action of phospholipases and the modulation of membrane curvature and curvature stress resulting from this activity. The alteration of the tridimensional structure of membranes upon the action of phospholipases is analyzed based [...] Read more.
In this revision work, we emphasize the close relationship between the action of phospholipases and the modulation of membrane curvature and curvature stress resulting from this activity. The alteration of the tridimensional structure of membranes upon the action of phospholipases is analyzed based on studies on model lipid membranes. The transient unbalance of both compositional and physical membrane properties between the hemilayers upon phospholipase activity lead to curvature tension and the catalysis of several membrane-related processes. Several proteins’ membrane-bound and soluble forms are susceptible to regulation by the curvature stress induced by phospholipase action, which has important consequences in cell signaling. Additionally, the modulation of membrane fusion by phospholipase products regulates membrane dynamics in several cellular scenarios. We commented on vesicle fusion in the Golgi-endoplasmic system, synaptic vesicle fusion to the plasma membrane, viral membrane fusion to host cell plasma membrane and gametes membrane fusion upon acrosomal reaction. Furthermore, we explored the modulation of membrane fusion by the asymmetric adsorption of amphiphilic drugs. A deep understanding of the relevance of lipid membrane structure, particularly membrane curvature and curvature stress, on different cellular events leads to the challenge of its regulation, which may become a powerful tool for pharmacological therapy. Full article
(This article belongs to the Special Issue Recent Studies on the Behaviour of Lipid Membranes)
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15 pages, 1523 KiB  
Review
Red Blood Cell Membrane Cholesterol May Be a Key Regulator of Sickle Cell Disease Microvascular Complications
by Eric J. Niesor, Elie Nader, Anne Perez, François Lamour, Renée Benghozi, Alan Remaley, Swee Lay Thein and Philippe Connes
Membranes 2022, 12(11), 1134; https://doi.org/10.3390/membranes12111134 - 11 Nov 2022
Cited by 6 | Viewed by 2879
Abstract
Cell membrane lipid composition, especially cholesterol, affects many functions of embedded enzymes, transporters and receptors in red blood cells (RBC). High membrane cholesterol content affects the RBCs’ main vital function, O2 and CO2 transport and delivery, with consequences on peripheral tissue [...] Read more.
Cell membrane lipid composition, especially cholesterol, affects many functions of embedded enzymes, transporters and receptors in red blood cells (RBC). High membrane cholesterol content affects the RBCs’ main vital function, O2 and CO2 transport and delivery, with consequences on peripheral tissue physiology and pathology. A high degree of deformability of RBCs is required to accommodate the size of micro-vessels with diameters significantly lower than RBCs. The potential therapeutic role of high-density lipoproteins (HDL) in the removal of cholesterol and its activity regarding maintenance of an optimal concentration of RBC membrane cholesterol have not been well investigated. On the contrary, the focus for HDL research has mainly been on the clearance of cholesterol accumulated in atherosclerotic macrophages and plaques. Since all interventions aiming at decreasing cardiovascular diseases by increasing the plasma level of HDL cholesterol have failed so far in large outcome studies, we reviewed the potential role of HDL to remove excess membrane cholesterol from RBC, especially in sickle cell disease (SCD). Indeed, abundant literature supports a consistent decrease in cholesterol transported by all plasma lipoproteins in SCD, in addition to HDL, low- (LDL) and very low-density lipoproteins (VLDL). Unexpectedly, these decreases in plasma were associated with an increase in RBC membrane cholesterol. The concentration and activity of the main enzyme involved in the removal of cholesterol and generation of large HDL particles—lecithin cholesterol ester transferase (LCAT)—are also significantly decreased in SCD. These observations might partially explain the decrease in RBC deformability, diminished gas exchange and tendency of RBCs to aggregate in SCD. We showed that incubation of RBC from SCD patients with human HDL or the HDL-mimetic peptide Fx5A improves the impaired RBC deformability and decreases intracellular reactive oxygen species levels. We propose that the main physiological role of HDL is to regulate the cholesterol/phospholipid ratio (C/PL), which is fundamental to the transport of oxygen and its delivery to peripheral tissues. Full article
(This article belongs to the Special Issue Recent Studies on the Behaviour of Lipid Membranes)
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