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Membranes
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Advances in Model Membrane Systems
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Advances in Model Membrane Systems

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

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 20903

Special Issue Editor

Dr. Hsin-Hui Shen

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, Monash University, Melbourne 3800, Australia
Interests: bacterial membrane preparations; membrane surface functionlization; QCM-D; neutron reflectometry; membrane proteins

Special Issue Information

Dear Colleagues,

Cellular membranes regulate biological process and play a central role in the cell response. The complexity of biological membranes has led to the development of a range of simpler membrane model systems to precisely control the size, geometry and membrane compositions. Model membrane systems are then widely applied to probe the behaviour of protein, drugs, peptides and nanoparticles in a membrane.  In the past decades, membrane models such as monolayer, supported lipid bilayer, nanodiscs and hybrid lipid-polymer bilayers have attracted enormous interests for many researchers from different fields to understand the interaction mechanism of biomolecules and/or drug carriers with the membrane. Membrane modelling covers both prokaryotic (bacteria) and eukaryotic cells. In light of the current knowledge and engineering technologies, a wide variety of simpler membrane model systems have been developed to mimetic the cellular membranes in solution or on a substrate.

The aim of this Special Issue is to cover novel research trends in the development of new membrane models or the use of membrane models for biological applications. We request submissions that provide insights into the fundamental of membrane model design, characterization and their applications. These membrane models can either be monolayer, nanodiscs, supported bilayer and hybrid membrane systems. The contributions can be original research papers, reviews and methodological developments. Areas to be covered may include, but are not limited to:

  • Development and characterization of the membrane models (artificial generated supported lipid bilayer, monolayer, nanodiscs and hybrid lipid-polymer bilayer)
  • Application of membrane models to various biological systems including but not limited to:
    • Interaction of bacterial membrane model with antibiotics,
    • Targeting proteins positions in membrane bilayer,
    • Interaction between nanoparticles and membranes,
    • Drugs and nanocarriers interaction with membrane targets.
  • Analysis of membrane models using quartz crystal microbalance with dissipation (QCM-D), neutron reflectometry, atomic force microscope (AFM), surface plasmon resonance (SPR) and other advanced surface characterization techniques.

I look forward to receiving your contributions. 

Dr. Hsin-Hui Shen
Guest Editor

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

  • membrane preparation
  • membrane surface functionalization
  • monolayer
  • bilayer
  • liposomes
  • nanodiscs
  • hybrid lipid-polymer bilayer
  • biosensor

Published Papers (10 papers)

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Research

Jump to: Review

17 pages, 4565 KiB  
Article
Physicochemical Characteristics of Model Membranes Composed of Legionella gormanii Lipids
by Katarzyna Pastuszak, Elżbieta Chmiel, Bożena Kowalczyk, Jacek Tarasiuk, Małgorzata Jurak and Marta Palusińska-Szysz
Membranes 2023, 13(3), 356; https://doi.org/10.3390/membranes13030356 - 20 Mar 2023
Cited by 3 | Viewed by 1575
Abstract
Legionella gormanii is one of the species belonging to the genus Legionella, which causes atypical community-acquired pneumonia. The most important virulence factors that enable the bacteria to colonize the host organism are associated with the cell surface. Lipids building the cell envelope [...] Read more.
Legionella gormanii is one of the species belonging to the genus Legionella, which causes atypical community-acquired pneumonia. The most important virulence factors that enable the bacteria to colonize the host organism are associated with the cell surface. Lipids building the cell envelope are crucial not only for the membrane integrity of L. gormanii but also by virtue of being a dynamic site of interactions between the pathogen and the metabolites supplied by its host. The utilization of exogenous choline by the Legionella species results in changes in the lipids’ composition, which influences the physicochemical properties of the cell surface. The aim of this study was to characterize the interfacial properties of the phospholipids extracted from L. gormanii cultured with (PL+choline) and without exogenous choline (PL−choline). The Langmuir monolayer technique coupled with the surface potential (SPOT) sensor and the Brewster angle microscope (BAM) made it possible to prepare the lipid monomolecular films (model membranes) and study their properties at the liquid/air interface at 20 °C and 37 °C. The results indicate the effect of the choline addition to the bacterial medium on the properties of the L. gormanii phospholipid membranes. The differences were revealed in the organization of monolayers, their molecular packing and ordering, degree of condensation and changes in the components’ miscibility. These findings are the basis for further research on the mechanisms of adaptation of this pathogen, which by changing the native composition and properties of lipids, bypasses the action of antimicrobial compounds and avoids the host immune attack. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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12 pages, 5743 KiB  
Article
Odor Discrimination by Lipid Membranes
by Troy W. Lowry, Aubrey E. Kusi-Appiah, Debra Ann Fadool and Steven Lenhert
Membranes 2023, 13(2), 151; https://doi.org/10.3390/membranes13020151 - 24 Jan 2023
Cited by 6 | Viewed by 1739
Abstract
Odor detection and discrimination in mammals is known to be initiated by membrane-bound G-protein-coupled receptors (GPCRs). The role that the lipid membrane may play in odor discrimination, however, is less well understood. Here, we used model membrane systems to test the hypothesis that [...] Read more.
Odor detection and discrimination in mammals is known to be initiated by membrane-bound G-protein-coupled receptors (GPCRs). The role that the lipid membrane may play in odor discrimination, however, is less well understood. Here, we used model membrane systems to test the hypothesis that phospholipid bilayer membranes may be capable of odor discrimination. The effect of S-carvone, R-carvone, and racemic lilial on the model membrane systems was investigated. The odorants were found to affect the fluidity of supported lipid bilayers as measured by fluorescence recovery after photobleaching (FRAP). The effect of odorants on surface-supported lipid multilayer microarrays of different dimensions was also investigated. The lipid multilayer micro- and nanostructure was highly sensitive to exposure to these odorants. Fluorescently-labeled lipid multilayer droplets of 5-micron diameter were more responsive to these odorants than ethanol controls. Arrays of lipid multilayer diffraction gratings distinguished S-carvone from R-carvone in an artificial nose assay. Our results suggest that lipid bilayer membranes may play a role in odorant discrimination and molecular recognition in general. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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14 pages, 3514 KiB  
Article
Evaluation of Cell-Free Synthesized Human Channel Proteins for In Vitro Channel Research
by Rei Nishiguchi, Toyohisa Tanaka, Jun Hayashida, Tomoya Nakagita, Wei Zhou and Hiroyuki Takeda
Membranes 2023, 13(1), 48; https://doi.org/10.3390/membranes13010048 - 30 Dec 2022
Cited by 5 | Viewed by 2220
Abstract
Despite channel proteins being important drug targets, studies on channel proteins remain limited, as the proteins are difficult to express and require correct complex formation within membranes. Although several in vitro synthesized recombinant channels have been reported, considering the vast diversity of the [...] Read more.
Despite channel proteins being important drug targets, studies on channel proteins remain limited, as the proteins are difficult to express and require correct complex formation within membranes. Although several in vitro synthesized recombinant channels have been reported, considering the vast diversity of the structures and functions of channel proteins, it remains unclear which classes of channels cell-free synthesis can be applied to. In this study, we synthesized 250 clones of human channels, including ion channel pore-forming subunits, gap junction proteins, porins, and regulatory subunits, using a wheat cell-free membrane protein production system, and evaluated their synthetic efficiency and function. Western blotting confirmed that 95% of the channels were successfully synthesized, including very large channels with molecular weights of over 200 kDa. A subset of 47 voltage-gated potassium ion channels was further analyzed using a planar lipid bilayer assay, out of which 80% displayed a voltage-dependent opening in the assay. We co-synthesized KCNB1 and KCNS3, a known heteromeric complex pair, and demonstrated that these channels interact on a liposome. These results indicate that cell-free protein synthesis provides a promising solution for channel studies to overcome the bottleneck of in vitro protein production. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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13 pages, 4256 KiB  
Article
In-Depth Analysis of the Extracorporeal Proteome Adsorbed to Dialysis Membranes during Hemodialysis
by Lisa Daniel-Fischer, Isabel J. Sobieszek, Anja Wagner, Juan Manuel Sacnun, Bruno Watschinger, Christoph Aufricht, Klaus Kratochwill and Rebecca Herzog
Membranes 2022, 12(11), 1120; https://doi.org/10.3390/membranes12111120 - 09 Nov 2022
Cited by 1 | Viewed by 1223
Abstract
Used hemodialysis membranes (HD-M) are a valuable reservoir of biological information. Proteins bind to HD-M, but whether this process depends on the type of membrane or patient factors or selectively affects specific protein classes has not been adequately elucidated. State-of-the-art proteomics techniques are [...] Read more.
Used hemodialysis membranes (HD-M) are a valuable reservoir of biological information. Proteins bind to HD-M, but whether this process depends on the type of membrane or patient factors or selectively affects specific protein classes has not been adequately elucidated. State-of-the-art proteomics techniques are capable of identifying and quantifying this therapy-specific subproteome to enable the analysis of disease- or membrane-induced pathophysiologies. We demonstrate the feasibility of the deep proteomic characterization of the extracorporeal proteome adsorbed to HD-M. A shotgun proteomics approach using nano-flow liquid chromatography coupled to mass-spectrometry identified 1648 unique proteins eluted by a chaotropic buffer from the HD-M of eight patients. In total, 995 proteins were present in all eluates; a more stringent approach showed that a core proteome of 310 proteins could be identified independently in all samples. Stability of the dialyzer proteome was demonstrated by a >90% re-identification rate on longitudinal samples of a single patient. The core proteome showed an overrepresentation of pathways of hemostasis and the immune system, and showed differences in membrane materials (polysulfone vs. helixone). This study demonstrates that optimized conditions combined with high-performance proteomics enable the in-depth exploration of the subproteome bound to HD-M, yielding a stable core proteome that can be exploited to study patient-specific factors and improve hemodialysis therapy. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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20 pages, 17943 KiB  
Article
A Lagrangian Thin-Shell Finite Element Method for Interacting Particles on Fluid Membranes
by Sanjay Dharmavaram, Xinran Wan and Luigi E. Perotti
Membranes 2022, 12(10), 960; https://doi.org/10.3390/membranes12100960 - 30 Sep 2022
Cited by 1 | Viewed by 1570
Abstract
A recurring motif in soft matter and biophysics is modeling the mechanics of interacting particles on fluid membranes. One of the main outstanding challenges in these applications is the need to model the strong coupling between the substrate deformation and the particles’ positions [...] Read more.
A recurring motif in soft matter and biophysics is modeling the mechanics of interacting particles on fluid membranes. One of the main outstanding challenges in these applications is the need to model the strong coupling between the substrate deformation and the particles’ positions as the latter freely move on the former. This work presents a thin-shell finite element formulation based on subdivision surfaces to compute equilibrium configurations of a thin fluid shell with embedded particles. We use a variational Lagrangian framework to couple the mechanics of the particles and the substrate without having to resort to ad hoc constraints to anchor the particles to the surface. Unlike established methods for such systems, the particles are allowed to move between elements of the finite element mesh. This is achieved by parametrizing the particle locations on the reference configuration. Using the Helfrich–Canham energy as a model for fluid shells, we present the finite element method’s implementation and an efficient search algorithm required to locate particles on the reference mesh. Several analyses with varying numbers of particles are finally presented reproducing symmetries observed in the classic Thomson problem and showcasing the coupling between interacting particles and deformable membranes. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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12 pages, 2158 KiB  
Article
Control of Line Tension at Phase-Separated Lipid Domain Boundaries: Monounsaturated Fatty Acids with Different Chain Lengths and Osmotic Pressure
by Nichaporn Wongsirojkul, Aiko Masuta, Naofumi Shimokawa and Masahiro Takagi
Membranes 2022, 12(8), 781; https://doi.org/10.3390/membranes12080781 - 14 Aug 2022
Cited by 2 | Viewed by 1647
Abstract
Line tension at phase-separated lipid domain boundaries is an important factor that governs the stability of the phase separation. We studied the control of the line tension in lipid membranes composed of dioleoylphosphocholine (DOPC), dipalmitoylphosphocholine (DPPC), and cholesterol (Chol) by the addition of [...] Read more.
Line tension at phase-separated lipid domain boundaries is an important factor that governs the stability of the phase separation. We studied the control of the line tension in lipid membranes composed of dioleoylphosphocholine (DOPC), dipalmitoylphosphocholine (DPPC), and cholesterol (Chol) by the addition of the following three monounsaturated fatty acids (MUFAs) with different chain lengths: palmitoleic acid (PaA), oleic acid (OA), and eicosenoic acid (EiA). In addition, we attempted to alter the line tension by applying osmotic pressure. The phase behavior of the MUFA-containing lipid membranes in the presence and absence of osmotic stress was observed by fluorescence and confocal laser scanning microscopy. The line tension was quantitatively measured from the domain boundary fluctuation by flicker spectroscopy, and the interactions between the lipids and MUFAs were examined by differential scanning calorimetry. PaA and OA, which are shorter MUFAs, decreased the line tension, whereas EiA changed the liquid domain to a solid domain. The osmotic pressure increased the line tension, even in the presence of MUFAs. It may be possible to control the line tension by combining the chemical approach of MUFA addition and the physical approach of applying osmotic pressure. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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16 pages, 6240 KiB  
Article
Aptamer-Modified Erythrocyte Membrane-Coated pH-Sensitive Nanoparticles for c-Met-Targeted Therapy of Glioblastoma Multiforme
by Xianping Liu, Yixin Chen, Daoying Geng, Haichun Li, Ting Jiang, Zimiao Luo, Jianhong Wang, Zhiqing Pang and Jun Zhang
Membranes 2022, 12(8), 744; https://doi.org/10.3390/membranes12080744 - 29 Jul 2022
Cited by 5 | Viewed by 1879
Abstract
Biomimetic drug delivery systems, especially red blood cell (RBC) membrane-based nanoparticle drug delivery systems (RNP), have been extensively utilized in tumor drug delivery because of their excellent biocompatibility and prolonged circulation. In this study, we developed an active targeting pH-sensitive RNP loaded with [...] Read more.
Biomimetic drug delivery systems, especially red blood cell (RBC) membrane-based nanoparticle drug delivery systems (RNP), have been extensively utilized in tumor drug delivery because of their excellent biocompatibility and prolonged circulation. In this study, we developed an active targeting pH-sensitive RNP loaded with DOX by decorating an aptamer SL1 on RBC membranes (SL1-RNP-DOX) for c-Met-targeted therapy of glioblastoma multiforme (GBM). SL1 could specifically bind to c-Met, which is highly expressed in GBM U87MG cells and facilitate DOX delivery to GBM cells. In vitro studies demonstrated that U87MG cells had a higher uptake of SL1-RNP-DOX (3.25 folds) and a stronger pro-apoptosis effect than unmodified RNP-DOX. In vivo fluorescence imaging and tissue distribution further demonstrated the higher tumor distribution of SL1-RNP-DOX (2.17 folds) compared with RNP-DOX. As a result, SL1-RNP-DOX presented the best anti-GBM effect with a prolonged median survival time (23 days vs. 15.5 days) and the strongest tumor cell apoptosis in vivo among all groups. In conclusion, SL1-RNP-DOX exhibited a promising targeting delivery strategy for GBM therapy. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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13 pages, 3232 KiB  
Communication
An AFM Approach Applied in a Study of α-Crystallin Membrane Association: New Insights into Lens Hardening and Presbyopia Development
by Nawal K. Khadka, Raju Timsina and Laxman Mainali
Membranes 2022, 12(5), 522; https://doi.org/10.3390/membranes12050522 - 14 May 2022
Cited by 5 | Viewed by 2238
Abstract
The lens of the eye loses elasticity with age, while α-crystallin association with the lens membrane increases with age. It is unclear whether there is any correlation between α-crystallin association with the lens membrane and loss in lens elasticity. This research investigated α-crystallin [...] Read more.
The lens of the eye loses elasticity with age, while α-crystallin association with the lens membrane increases with age. It is unclear whether there is any correlation between α-crystallin association with the lens membrane and loss in lens elasticity. This research investigated α-crystallin membrane association using atomic force microscopy (AFM) for the first time to study topographical images and mechanical properties (breakthrough force and membrane area compressibility modulus (KA), as measures of elasticity) of the membrane. α-Crystallin extracted from the bovine lens cortex was incubated with a supported lipid membrane (SLM) prepared on a flat mica surface. The AFM images showed the time-dependent interaction of α-crystallin with the SLM. Force spectroscopy revealed the presence of breakthrough events in the force curves obtained in the membrane regions where no α-crystallin was associated, which suggests that the membrane’s elasticity was maintained. The force curves in the α-crystallin submerged region and the close vicinity of the α-crystallin associated region in the membrane showed no breakthrough event within the defined peak force threshold, indicating loss of membrane elasticity. Our results showed that the association of α-crystallin with the membrane deteriorates membrane elasticity, providing new insights into understanding the molecular basis of lens hardening and presbyopia. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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Review

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16 pages, 1278 KiB  
Review
Impact of Hydrophilic Modification of Synthetic Dialysis Membranes on Hemocompatibility and Performance
by Adam M. Zawada, Thomas Lang, Bertram Ottillinger, Fatih Kircelli, Manuela Stauss-Grabo and James P. Kennedy
Membranes 2022, 12(10), 932; https://doi.org/10.3390/membranes12100932 - 26 Sep 2022
Cited by 11 | Viewed by 3014
Abstract
The dialyzer is the core element in the hemodialysis treatment of patients with end-stage kidney disease (ESKD). During hemodialysis treatment, the dialyzer replaces the function of the kidney by removing small and middle-molecular weight uremic toxins, while retaining essential proteins. Meanwhile, a dialyzer [...] Read more.
The dialyzer is the core element in the hemodialysis treatment of patients with end-stage kidney disease (ESKD). During hemodialysis treatment, the dialyzer replaces the function of the kidney by removing small and middle-molecular weight uremic toxins, while retaining essential proteins. Meanwhile, a dialyzer should have the best possible hemocompatibility profile as the perpetuated contact of blood with artificial surfaces triggers complement activation, coagulation and immune cell activation, and even low-level activation repeated chronically over years may lead to undesired effects. During hemodialysis, the adsorption of plasma proteins to the dialyzer membrane leads to a formation of a secondary membrane, which can compromise both the uremic toxin removal and hemocompatibility of the dialyzer. Hydrophilic modifications of novel dialysis membranes have been shown to reduce protein adsorption, leading to better hemocompatibility profile and performance stability during dialysis treatments. This review article focuses on the importance of performance and hemocompatibility of dialysis membranes for the treatment of dialysis patients and summarizes recent studies on the impact of protein adsorption and hydrophilic modifications of membranes on these two core elements of a dialyzer. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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29 pages, 2698 KiB  
Review
Solid and Liquid Surface-Supported Bacterial Membrane Mimetics as a Platform for the Functional and Structural Studies of Antimicrobials
by Shiqi Li, Ruohua Ren, Letian Lyu, Jiangning Song, Yajun Wang, Tsung-Wu Lin, Anton Le Brun, Hsien-Yi Hsu and Hsin-Hui Shen
Membranes 2022, 12(10), 906; https://doi.org/10.3390/membranes12100906 - 20 Sep 2022
Cited by 5 | Viewed by 2188
Abstract
Increasing antibiotic resistance has provoked the urgent need to investigate the interactions of antimicrobials with bacterial membranes. The reasons for emerging antibiotic resistance and innovations in novel therapeutic approaches are highly relevant to the mechanistic interactions between antibiotics and membranes. Due to the [...] Read more.
Increasing antibiotic resistance has provoked the urgent need to investigate the interactions of antimicrobials with bacterial membranes. The reasons for emerging antibiotic resistance and innovations in novel therapeutic approaches are highly relevant to the mechanistic interactions between antibiotics and membranes. Due to the dynamic nature, complex compositions, and small sizes of native bacterial membranes, bacterial membrane mimetics have been developed to allow for the in vitro examination of structures, properties, dynamics, and interactions. In this review, three types of model membranes are discussed: monolayers, supported lipid bilayers, and supported asymmetric bilayers; this review highlights their advantages and constraints. From monolayers to asymmetric bilayers, biomimetic bacterial membranes replicate various properties of real bacterial membranes. The typical synthetic methods for fabricating each model membrane are introduced. Depending on the properties of lipids and their biological relevance, various lipid compositions have been used to mimic bacterial membranes. For example, mixtures of phosphatidylethanolamines (PE), phosphatidylglycerols (PG), and cardiolipins (CL) at various molar ratios have been used, approaching actual lipid compositions of Gram-positive bacterial membranes and inner membranes of Gram-negative bacteria. Asymmetric lipid bilayers can be fabricated on solid supports to emulate Gram-negative bacterial outer membranes. To probe the properties of the model bacterial membranes and interactions with antimicrobials, three common characterization techniques, including quartz crystal microbalance with dissipation (QCM-D), surface plasmon resonance (SPR), and neutron reflectometry (NR) are detailed in this review article. Finally, we provide examples showing that the combination of bacterial membrane models and characterization techniques is capable of providing crucial information in the design of new antimicrobials that combat bacterial resistance. Full article
(This article belongs to the Special Issue Advances in Model Membrane Systems)
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