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Membranes
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Advances in Membrane Lipid Replacement and Therapy
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Advances in Membrane Lipid Replacement and Therapy

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

Deadline for manuscript submissions: closed (15 September 2021) | Viewed by 28816

Special Issue Editors

Prof. Dr. Garth L. Nicolson

E-Mail Website1 Website2
Guest Editor
President, Chief Scientific Officer at Institute for Molecular Medicine, Huntington Beach, CA, USA
Interests: membranes; membrane lipid replacement; lipid bilayers; Mycoplasma; cellular biology; laboratory medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Pablo V. Escribá

E-Mail Website
Guest Editor
University of the Balearic Islands, Palma, Spain
Interests: membrane structure and function; membrane lipid replacement; membrane lipid therapy
Prof. Dr. Gonzalo Ferreira de Mattos

E-Mail Website
Guest Editor
Laboratory of Biological Membranes, Ion Channels, and Cell Signaling, Chairman Departamento de Biofisica, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
Interests: membrane lipid replacement; ion channels; intracellular calcium; heart, neurons; sperm; electrophysiology

Special Issue Information

Dear Colleagues,

Phospholipid bilayers are the basic matrix of all biological membranes, and they are indispensable barriers and form essential cellular compartments for organelles and separation of important chemical and enzymatic reactions. They also function as structural supports for signaling platforms, enzymatic and redox complexes, membrane channels and electrical properties, cytoskeletal attachments, adhesion and recognition complexes, cell transport and elimination systems, and energy storage reservoirs, among other essential cellular functions. They are also important structural elements in lipid–protein complexes, such as lipoproteins and other cellular lipid complexes, and are essential in the dynamic properties of cellular membranes embodied in the fluid–mosaic membrane structure.

During stress, illness, and aging, dietary sources of membrane lipids alone often cannot provide enough essential membrane lipids for the maintenance of cellular health and function. This is particularly important for individuals who have chronic or acute illnesses where membrane lipids are not in balance (dyslipidemia) or are at particular risk for damage or alterations that cause loss of function. Thus, membrane lipids under these conditions must be rebalanced in composition, repaired or replaced in order to retain essential cellular functions.  

Supplemental membrane lipids and phospholipids have been used as supportive, safe strategies for the health maintenance, aging, and treatment of health conditions where cellular membranes are damaged or their lipid constituents removed or where dyslipidemia occurs. In addition, membrane lipids have been used as therapeutic tools in order to improve function or to inhibit deleterious processes. Thus, the use of existing membrane lipids or the development of new bioactive lipid derivatives have been exploited for the treatment of various clinical conditions, such as cancer, neurodegenerative disease, metabolic disease, autoimmune disease, cardiovascular disease and infections, and other conditions.

This Special Issue will focus on membrane lipid replacement and its therapeutic use in replacing damaged membrane lipids in order to restore cell membrane and intracellular membrane function and increase our knowledge of cellular and membrane structure, function, and dynamics. The membrane systems of cells are fully integrated, and they communicate, fuse, and exchange lipids with other membranes and also trade lipids with cellular structures such as lipoproteins, lipid droplets, globules, micelles, and chylomicrons. This issue will explore recent progress in the use of dietary supplements containing membrane lipids and the development of new bioactive lipid derivatives in order to therapeutically improve health outcomes.

Prof. Dr. Garth L. Nicolson
Prof. Dr. Pablo V. Escribá
Prof. Dr. Gonzalo Ferreira de Mattos
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

  • Biological membranes
  • Membrane lipid replacement
  • Innovations in therapeutics
  • Membrane–protein interactions
  • Biological membranes and cell signaling
  • Lipid therapeutics
  • Ion channels
  • Chronic illnesses and membrane lipids
  • Mitochondrial function
  • Membrane structure and function
  • Membrane lipid therapy
  • Melitherapy

Published Papers (4 papers)

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Review

19 pages, 1063 KiB  
Review
A Brief Introduction to Some Aspects of the Fluid–Mosaic Model of Cell Membrane Structure and Its Importance in Membrane Lipid Replacement
by Garth L. Nicolson and Gonzalo Ferreira de Mattos
Membranes 2021, 11(12), 947; https://doi.org/10.3390/membranes11120947 - 29 Nov 2021
Cited by 23 | Viewed by 8262
Abstract
Early cell membrane models placed most proteins external to lipid bilayers in trimolecular structures or as modular lipoprotein units. These thermodynamically untenable structures did not allow lipid lateral movements independent of membrane proteins. The Fluid–Mosaic Membrane Model accounted for these and other properties, [...] Read more.
Early cell membrane models placed most proteins external to lipid bilayers in trimolecular structures or as modular lipoprotein units. These thermodynamically untenable structures did not allow lipid lateral movements independent of membrane proteins. The Fluid–Mosaic Membrane Model accounted for these and other properties, such as membrane asymmetry, variable lateral mobilities of membrane components and their associations with dynamic complexes. Integral membrane proteins can transform into globular structures that are intercalated to various degrees into a heterogeneous lipid bilayer matrix. This simplified version of cell membrane structure was never proposed as the ultimate biomembrane description, but it provided a basic nanometer scale framework for membrane organization. Subsequently, the structures associated with membranes were considered, including peripheral membrane proteins, and cytoskeletal and extracellular matrix components that restricted lateral mobility. In addition, lipid–lipid and lipid–protein membrane domains, essential for cellular signaling, were proposed and eventually discovered. The presence of specialized membrane domains significantly reduced the extent of the fluid lipid matrix, so membranes have become more mosaic with some fluid areas over time. However, the fluid regions of membranes are very important in lipid transport and exchange. Various lipid globules, droplets, vesicles and other membranes can fuse to incorporate new lipids or expel damaged lipids from membranes, or they can be internalized in endosomes that eventually fuse with other internal vesicles and membranes. They can also be externalized in a reverse process and released as extracellular vesicles and exosomes. In this Special Issue, the use of membrane phospholipids to modify cellular membranes in order to modulate clinically relevant host properties is considered. Full article
(This article belongs to the Special Issue Advances in Membrane Lipid Replacement and Therapy)
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39 pages, 1015 KiB  
Review
Fundamentals of Membrane Lipid Replacement: A Natural Medicine Approach to Repairing Cellular Membranes and Reducing Fatigue, Pain, and Other Symptoms While Restoring Function in Chronic Illnesses and Aging
by Garth L. Nicolson, Gonzalo Ferreira de Mattos, Michael Ash, Robert Settineri and Pablo V. Escribá
Membranes 2021, 11(12), 944; https://doi.org/10.3390/membranes11120944 - 29 Nov 2021
Cited by 12 | Viewed by 7684
Abstract
Membrane Lipid Replacement (MLR) uses natural membrane lipid supplements to safely replace damaged, oxidized lipids in membranes in order to restore membrane function, decrease symptoms and improve health. Oral MLR supplements contain mixtures of cell membrane glycerolphospholipids, fatty acids, and other lipids, and [...] Read more.
Membrane Lipid Replacement (MLR) uses natural membrane lipid supplements to safely replace damaged, oxidized lipids in membranes in order to restore membrane function, decrease symptoms and improve health. Oral MLR supplements contain mixtures of cell membrane glycerolphospholipids, fatty acids, and other lipids, and can be used to replace and remove damaged cellular and intracellular membrane lipids. Membrane injury, caused mainly by oxidative damage, occurs in essentially all chronic and acute medical conditions, including cancer and degenerative diseases, and in normal processes, such as aging and development. After ingestion, the protected MLR glycerolphospholipids and other lipids are dispersed, absorbed, and internalized in the small intestines, where they can be partitioned into circulating lipoproteins, globules, liposomes, micelles, membranes, and other carriers and transported in the lymphatics and blood circulation to tissues and cellular sites where they are taken in by cells and partitioned into various cellular membranes. Once inside cells, the glycerolphospholipids and other lipids are transferred to various intracellular membranes by lipid carriers, globules, liposomes, chylomicrons, or by direct membrane–membrane interactions. The entire process appears to be driven by ‘bulk flow’ or mass action principles, where surplus concentrations of replacement lipids can stimulate the natural exchange and removal of damaged membrane lipids while the replacement lipids undergo further enzymatic alterations. Clinical studies have demonstrated the advantages of MLR in restoring membrane and organelle function and reducing fatigue, pain, and other symptoms in chronic illness and aging patients. Full article
(This article belongs to the Special Issue Advances in Membrane Lipid Replacement and Therapy)
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45 pages, 2683 KiB  
Review
Lipids in Pathophysiology and Development of the Membrane Lipid Therapy: New Bioactive Lipids
by Manuel Torres, Sebastià Parets, Javier Fernández-Díaz, Roberto Beteta-Göbel, Raquel Rodríguez-Lorca, Ramón Román, Victoria Lladó, Catalina A. Rosselló, Paula Fernández-García and Pablo V. Escribá
Membranes 2021, 11(12), 919; https://doi.org/10.3390/membranes11120919 - 24 Nov 2021
Cited by 15 | Viewed by 5146
Abstract
Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy [...] Read more.
Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy source, lipids have important structural and functional roles, e.g., fatty acyl moieties in phospholipids have distinct impacts on human health depending on their saturation, carbon length, and isometry. These and other membrane lipids have quite specific effects on the lipid bilayer structure, which regulates the interaction with signaling proteins. Alterations to lipids have been associated with important diseases, and, consequently, normalization of these alterations or regulatory interventions that control membrane lipid composition have therapeutic potential. This approach, termed membrane lipid therapy or membrane lipid replacement, has emerged as a novel technology platform for nutraceutical interventions and drug discovery. Several clinical trials and therapeutic products have validated this technology based on the understanding of membrane structure and function. The present review analyzes the molecular basis of this innovative approach, describing how membrane lipid composition and structure affects protein-lipid interactions, cell signaling, disease, and therapy (e.g., fatigue and cardiovascular, neurodegenerative, tumor, infectious diseases). Full article
(This article belongs to the Special Issue Advances in Membrane Lipid Replacement and Therapy)
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18 pages, 1593 KiB  
Review
Plasmalogen Replacement Therapy
by José Carlos Bozelli, Jr. and Richard M. Epand
Membranes 2021, 11(11), 838; https://doi.org/10.3390/membranes11110838 - 29 Oct 2021
Cited by 17 | Viewed by 6893
Abstract
Plasmalogens, a subclass of glycerophospholipids containing a vinyl-ether bond, are one of the major components of biological membranes. Changes in plasmalogen content and molecular species have been reported in a variety of pathological conditions ranging from inherited to metabolic and degenerative diseases. Most [...] Read more.
Plasmalogens, a subclass of glycerophospholipids containing a vinyl-ether bond, are one of the major components of biological membranes. Changes in plasmalogen content and molecular species have been reported in a variety of pathological conditions ranging from inherited to metabolic and degenerative diseases. Most of these diseases have no treatment, and attempts to develop a therapy have been focusing primarily on protein/nucleic acid molecular targets. However, recent studies have shifted attention to lipids as the basis of a therapeutic strategy. In these pathological conditions, the use of plasmalogen replacement therapy (PRT) has been shown to be a successful way to restore plasmalogen levels as well as to ameliorate the disease phenotype in different clinical settings. Here, the current state of PRT will be reviewed as well as a discussion of future perspectives in PRT. It is proposed that the use of PRT provides a modern and innovative molecular medicine approach aiming at improving health outcomes in different conditions with clinically unmet needs. Full article
(This article belongs to the Special Issue Advances in Membrane Lipid Replacement and Therapy)
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