Membrane Transport in Health and Disease: From Basic Science to Therapeutic Applications

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

Deadline for manuscript submissions: closed (20 January 2022) | Viewed by 26196

Special Issue Editor


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Guest Editor
Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Via Provinciale Lecce-Monteroni, I-73100 Lecce, Italy
Interests: metabolism; mitochondria; cell bioenergetics; mitochondrial carriers; mitochondrial diseases; cancer metabolism

Special Issue Information

Dear Colleagues,

Membrane transport proteins play crucial roles in cell physiology, metabolism, and signaling by facilitating translocation of solutes, including nutrients, metabolites, and inorganic ions, across biological membranes. Membrane transport proteins are essential for cell functions and metabolism, by maintaining homeostasis and assuring cell survival in response to both environmental and intracellular stress stimuli.

Interestingly, the failure of these systems could lead to the development of diseases; altered expression and function of some membrane transporters have been described in several disorders characterized by metabolic alterations.

Moreover, there is increasing evidence that membrane transport proteins also play key roles in pharmacology, affecting the entry of drugs into cells and extrusion of drugs from them. For this reason, they are of primary medical/pharmacological interest for target-oriented drug discovery and delivery.

The aim of this Special Issue is to provide an extensive coverage of recent advances in the field of membrane transport focusing on the emerging bridge between molecular structure and function of membrane transport proteins and their role in cell biology and physiology at tissue- or a whole-organism level.

A deeper investigation of the functional role of membrane transport proteins and of the structure–function relationships may allow the understanding of their role in contributing to pathologies and the development of improved pharmacological strategies.

This Special Issue welcomes both original research articles and comprehensive reviews. Short communications will also be considered.

Dr. Paola Lunetti
Guest Editor

Manuscript Submission Information

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Keywords

  • membrane transport proteins
  • transport proteins function and structure
  • cell membrane
  • organelle membranes
  • cellular function
  • cellular signaling
  • bioenergetics
  • transport protein diseases
  • drug targets

Published Papers (5 papers)

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Research

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13 pages, 6863 KiB  
Article
Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative
by Georgios Rossos, Sotiris K. Hadjikakou and Nikolaos Kourkoumelis
Membranes 2021, 11(10), 743; https://doi.org/10.3390/membranes11100743 - 28 Sep 2021
Cited by 4 | Viewed by 2999
Abstract
Benzimidazole derivatives have gained attention recently due to their wide pharmacological activity acting as anti-inflammatory, hypotensive, analgesic, and anti-aggregatory agents. They are also common ligands in transition metal coordination chemistry, forming complex compounds with enhanced biological properties, especially in targeted cancer therapy. A [...] Read more.
Benzimidazole derivatives have gained attention recently due to their wide pharmacological activity acting as anti-inflammatory, hypotensive, analgesic, and anti-aggregatory agents. They are also common ligands in transition metal coordination chemistry, forming complex compounds with enhanced biological properties, especially in targeted cancer therapy. A key issue to understand anti-tumour effects is drug permeability through cellular membranes, as poor permeability outcomes can avert further futile drug development. In this work, we conducted atomistic molecular dynamics (MD) simulations and biased MD simulations to explore the interactions of 2-benzimidazolyl-urea with a phospholipid bilayer (dipalmitoylphosphatidylcholine, DPPC) together with a previously synthesized copper(II) complex compound. The aim was to study the permeability of these compounds by assessing their free energy profile along the bilayer normal. The simulations indicated that both the ligand (2-benzimidazolyl-urea, BZIMU) and the complex show a similar behaviour, yielding high energy barriers for the permeation process. However, with increasing concentration of BZIMU, the molecules tend to aggregate and form a cluster, leading to the formation of a pore. Clustering and pore formation can possibly explain the previously observed cytotoxicity of the BZIMU molecule via membrane damage. Full article
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13 pages, 2158 KiB  
Article
Bioinformatic Analysis of ABCA1 Gene Expression in Smoking and Chronic Obstructive Pulmonary Disease
by Stanislav Kotlyarov and Anna Kotlyarova
Membranes 2021, 11(9), 674; https://doi.org/10.3390/membranes11090674 - 31 Aug 2021
Cited by 6 | Viewed by 2730
Abstract
Smoking is a key modifiable risk factor for developing the chronic obstructive pulmonary disease (COPD). When smoking, many processes, including the reverse transport of cholesterol mediated by the ATP binding cassette transporter A1 (ABCA1) protein are disrupted in the lungs. Changes in the [...] Read more.
Smoking is a key modifiable risk factor for developing the chronic obstructive pulmonary disease (COPD). When smoking, many processes, including the reverse transport of cholesterol mediated by the ATP binding cassette transporter A1 (ABCA1) protein are disrupted in the lungs. Changes in the cholesterol content in the lipid rafts of plasma membranes can modulate the function of transmembrane proteins localized in them. It is believed that this mechanism participates in increasing the inflammation in COPD. Methods: Bioinformatic analysis of datasets from Gene Expression Omnibus (GEO) was carried out. Gene expression data from datasets of alveolar macrophages and the epithelium of the respiratory tract in smokers and COPD patients compared with non-smokers were used for the analysis. To evaluate differentially expressed genes, bioinformatic analysis was performed in comparison groups using the limma package in R (v. 4.0.2), and the GEO2R and Phantasus tools (v. 1.11.0). Results: The conducted bioinformatic analysis showed changes in the expression of the ABCA1 gene associated with smoking. In the alveolar macrophages of smokers, the expression levels of ABCA1 were lower than in non-smokers. At the same time, in most of the airway epithelial datasets, gene expression did not show any difference between the groups of smokers and non-smokers. In addition, it was shown that the expression of ABCA1 in the epithelial cells of the trachea and large bronchi is higher than in small bronchi. Conclusions: The conducted bioinformatic analysis showed that smoking can influence the expression of the ABCA1 gene, thereby modulating lipid transport processes in macrophages, which are part of the mechanisms of inflammation development. Full article
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11 pages, 1359 KiB  
Article
Quantitative Analysis of the Membrane Affinity of Local Anesthetics Using a Model Cell Membrane
by Wanjae Choi, Hyunil Ryu, Ahmed Fuwad, Seulmini Goh, Chaoge Zhou, Jiwook Shim, Masahiro Takagi, Soonjo Kwon, Sun Min Kim and Tae-Joon Jeon
Membranes 2021, 11(8), 579; https://doi.org/10.3390/membranes11080579 - 30 Jul 2021
Cited by 4 | Viewed by 3572
Abstract
Local anesthesia is a drug that penetrates the nerve cell membrane and binds to the voltage gate sodium channel, inhibiting the membrane potential and neurotransmission. It is mainly used in clinical uses to address the pain of surgical procedures in the local area. [...] Read more.
Local anesthesia is a drug that penetrates the nerve cell membrane and binds to the voltage gate sodium channel, inhibiting the membrane potential and neurotransmission. It is mainly used in clinical uses to address the pain of surgical procedures in the local area. Local anesthetics (LAs), however, can be incorporated into the membrane, reducing the thermal stability of the membrane as well as altering membrane properties such as fluidity, permeability, and lipid packing order. The effects of LAs on the membrane are not yet fully understood, despite a number of previous studies. In particular, it is necessary to analyze which is the more dominant factor, the membrane affinity or the structural perturbation of the membrane. To analyze the effects of LAs on the cell membrane and compare the results with those from model membranes, morphological analysis and 50% inhibitory concentration (IC50) measurement of CCD-1064sk (fibroblast, human skin) membranes were carried out for lidocaine (LDC) and tetracaine (TTC), the most popular LAs in clinical use. Furthermore, the membrane affinity of the LAs was quantitatively analyzed using a colorimetric polydiacetylene assay, where the color shift represents their distribution in the membrane. Further, to confirm the membrane affinity and structural effects of the membranes, we performed an electrophysiological study using a model protein (gramicidin A, gA) and measured the channel lifetime of the model protein on the free-standing lipid bilayer according to the concentration of each LA. Our results show that when LAs interact with cell membranes, membrane affinity is a more dominant factor than steric or conformational effects of the membrane. Full article
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Review

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21 pages, 9623 KiB  
Review
The Distribution and Role of the CFTR Protein in the Intracellular Compartments
by Agnieszka Lukasiak and Miroslaw Zajac
Membranes 2021, 11(11), 804; https://doi.org/10.3390/membranes11110804 - 22 Oct 2021
Cited by 15 | Viewed by 6110
Abstract
Cystic fibrosis is a hereditary disease that mainly affects secretory organs in humans. It is caused by mutations in the gene encoding CFTR with the most common phenylalanine deletion at position 508. CFTR is an anion channel mainly conducting Cl across the [...] Read more.
Cystic fibrosis is a hereditary disease that mainly affects secretory organs in humans. It is caused by mutations in the gene encoding CFTR with the most common phenylalanine deletion at position 508. CFTR is an anion channel mainly conducting Cl across the apical membranes of many different epithelial cells, the impairment of which causes dysregulation of epithelial fluid secretion and thickening of the mucus. This, in turn, leads to the dysfunction of organs such as the lungs, pancreas, kidney and liver. The CFTR protein is mainly localized in the plasma membrane; however, there is a growing body of evidence that it is also present in the intracellular organelles such as the endosomes, lysosomes, phagosomes and mitochondria. Dysfunction of the CFTR protein affects not only the ion transport across the epithelial tissues, but also has an impact on the proper functioning of the intracellular compartments. The review aims to provide a summary of the present state of knowledge regarding CFTR localization and function in intracellular compartments, the physiological role of this localization and the consequences of protein dysfunction at cellular, epithelial and organ levels. An in-depth understanding of intracellular processes involved in CFTR impairment may reveal novel opportunities in pharmacological agents of cystic fibrosis. Full article
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22 pages, 4177 KiB  
Review
Specifically Targeted Transport of Plasma Membrane Transporters: From Potential Mechanisms for Regulating Cell Health or Disease to Applications
by Yeqing He, Guandi He and Tengbing He
Membranes 2021, 11(10), 736; https://doi.org/10.3390/membranes11100736 - 27 Sep 2021
Cited by 6 | Viewed by 7360
Abstract
Normal substrate transport and signal transmission are the premise to ensure the health of biological somatic cells. Therefore, a comprehensive understanding of the molecular mechanism of intercellular substrate transport is of great significance for clinical treatment. In order to better understand the membrane [...] Read more.
Normal substrate transport and signal transmission are the premise to ensure the health of biological somatic cells. Therefore, a comprehensive understanding of the molecular mechanism of intercellular substrate transport is of great significance for clinical treatment. In order to better understand the membrane protein through its interaction with receptors, to help maintain a healthy cell and the molecular mechanisms of disease, in this paper, we seek to clarify, first of all, the recognition mechanism for different types of membrane protein receptors; pathogen invasion using the transport pathway involved in the membrane; and the latest specific target sites of various kinds of membrane transport carriers; to provide an explanation and summary of the system. Secondly, the downstream receptor proteins and specific substrates of different membrane transporters were classified systematically; the functional differences of different subclasses and their relationship with intracellular transport disorders were analyzed to further explore the potential relationship between cell transport disorders and diseases. Finally, the paper summarizes the use of membrane transporter-specific targets for drug design and development from the latest research results; it points out the transporter-related results in disease treatment; the application prospects and the direction for drug development and disease treatment providing a new train of thought; also for disease-specific targeted therapy, it provides a certain reference value. Full article
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