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Article ; Online: The Fluid-Mosaic model of cell membranes: A brief introduction, historical features, some general principles, and its adaptation to current information.

Nicolson, Garth L / Ferreira de Mattos, Gonzalo

Biochimica et biophysica acta. Biomembranes

2023 Volume 1865, Issue 4, Page(s) 184135

Abstract: ... representation of cell membranes (Singer and Nicolson, 1972). The FMM model was based on some general principles ...

Abstract	The Fluid-Mosaic Membrane (FMM) model was originally proposed as a general, nanometer-scale representation of cell membranes (Singer and Nicolson, 1972). The FMM model was based on some general principles, such as thermodynamic considerations, intercalation of globular proteins into a lipid bilayer, independent protein and lipid dynamics, cooperativity and other characteristics. Other models had trimolecular structures or membrane globular lipoprotein units. These latter models were flawed, because they did not allow autonomous lipids, membrane domains or discrete lateral dynamics. The FMM model was also consistent with membrane asymmetry, cis- and trans-membrane linkages and associations of membrane components into multi-molecular complexes and domains. It has remained useful for explaining the basic organizational principles and properties of various biological membranes. New information has been added, such as membrane-associated cytoskeletal assemblies, extracellular matrix interactions, transmembrane controls, specialized lipid-protein domains that differ in compositions, rotational and lateral mobilities, lifetimes, functions, and other characteristics. The presence of dense, structured membrane domains has reduced significantly the extent of fluid-lipid membrane areas, and the FMM model is now considered to be more mosaic and dense than the original proposal.
MeSH term(s)	Membrane Lipids/chemistry ; Membrane Proteins/chemistry ; Cell Membrane/metabolism ; Lipid Bilayers/chemistry ; Extracellular Matrix
Chemical Substances	Membrane Lipids ; Membrane Proteins ; Lipid Bilayers
Language	English
Publishing date	2023-02-05
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamem.2023.184135
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Article: Fifty Years of the Fluid-Mosaic Model of Biomembrane Structure and Organization and Its Importance in Biomedicine with Particular Emphasis on Membrane Lipid Replacement.

Nicolson, Garth L / Ferreira de Mattos, Gonzalo

Biomedicines

2022 Volume 10, Issue 7

Abstract: The Fluid-Mosaic Model has been the accepted general or basic model for biomembrane structure and organization for the last 50 years. In order to establish a basic model for biomembranes, some general principles had to be established, such as ... ...

Abstract	The Fluid-Mosaic Model has been the accepted general or basic model for biomembrane structure and organization for the last 50 years. In order to establish a basic model for biomembranes, some general principles had to be established, such as thermodynamic assumptions, various molecular interactions, component dynamics, macromolecular organization and other features. Previous researchers placed most membrane proteins on the exterior and interior surfaces of lipid bilayers to form trimolecular structures or as lipoprotein units arranged as modular sheets. Such membrane models were structurally and thermodynamically unsound and did not allow independent lipid and protein lateral movements. The Fluid-Mosaic Membrane Model was the only model that accounted for these and other characteristics, such as membrane asymmetry, variable lateral movements of membrane components, cis- and transmembrane linkages and dynamic associations of membrane components into multimolecular complexes. The original version of the Fluid-Mosaic Membrane Model was never proposed as the ultimate molecular description of all biomembranes, but it did provide a basic framework for nanometer-scale biomembrane organization and dynamics. Because this model was based on available 1960s-era data, it could not explain all of the properties of various biomembranes discovered in subsequent years. However, the fundamental organizational and dynamic aspects of this model remain relevant to this day. After the first generation of this model was published, additional data on various structures associated with membranes were included, resulting in the addition of membrane-associated cytoskeletal, extracellular matrix and other structures, specialized lipid-lipid and lipid-protein domains, and other configurations that can affect membrane dynamics. The presence of such specialized membrane domains has significantly reduced the extent of the fluid lipid membrane matrix as first proposed, and biomembranes are now considered to be less fluid and more mosaic with some fluid areas, rather than a fluid matrix with predominantly mobile components. However, the fluid-lipid matrix regions remain very important in biomembranes, especially those involved in the binding and release of membrane lipid vesicles and the uptake of various nutrients. Membrane phospholipids can associate spontaneously to form lipid structures and vesicles that can fuse with various cellular membranes to transport lipids and other nutrients into cells and organelles and expel damaged lipids and toxic hydrophobic molecules from cells and tissues. This process and the clinical use of membrane phospholipid supplements has important implications for chronic illnesses and the support of healthy mitochondria, plasma membranes and other cellular membrane structures.
Language	English
Publishing date	2022-07-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10071711
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Article: Bacterial toxins and heart function: heat-labile

Ferreira, Gonzalo / Cardozo, Romina / Sastre, Santiago / Costa, Carlos / Santander, Axel / Chavarría, Luisina / Guizzo, Valentina / Puglisi, José / Nicolson, G L

Biophysical reviews

2023 Volume 15, Issue 4, Page(s) 447–473

Abstract: Bacterial toxins can cause cardiomyopathy, though it is not its most common cause. Some bacterial toxins can form pores in the membrane of cardiomyocytes, while others can bind to membrane receptors. Enterotoxigenic : Supplementary information: The ... ...

Abstract	Bacterial toxins can cause cardiomyopathy, though it is not its most common cause. Some bacterial toxins can form pores in the membrane of cardiomyocytes, while others can bind to membrane receptors. Enterotoxigenic Supplementary information: The online version contains supplementary material available at 10.1007/s12551-023-01100-6.
Language	English
Publishing date	2023-07-22
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2486483-3
ISSN	1867-2469 ; 1867-2450
ISSN (online)	1867-2469
ISSN	1867-2450
DOI	10.1007/s12551-023-01100-6
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Article ; Online: ECGVEDNET: A Variational Encoder-Decoder Network for ECG Delineation in Morphology Variant ECGs.

Chen, Long / Jiang, Zheheng / Barker, Joseph / Zhou, Huiyu / Schlindwein, Fernando S / Nicolson, Will / Ng, G Andre / Li, Xin

IEEE transactions on bio-medical engineering

2024 Volume PP

Abstract: Electrocardiogram (ECG) delineation to identify the fiducial points of ECG segments, plays an important role in cardiovascular diagnosis and care. Whilst deep delineation frameworks have been deployed within the literature, several factors still hinder ... ...

Abstract	Electrocardiogram (ECG) delineation to identify the fiducial points of ECG segments, plays an important role in cardiovascular diagnosis and care. Whilst deep delineation frameworks have been deployed within the literature, several factors still hinder their development: (a) data availability: the capacity of deep learning models to generalise is limited by the amount of available data; (b) morphology variations: ECG complexes vary, even within the same person, which degrades the performance of conventional deep learning models. To address these concerns, we present a large-scale 12-leads ECG dataset, ICDIRS, to train and evaluate a novel deep delineation model-ECGVEDNET. ICDIRS is a large-scale ECG dataset with 156,145 QRS onset annotations and 156,145 T peak annotations. ECGVEDNET is a novel variational encoder-decoder network designed to address morphology variations. In ECGVEDNET, we construct a well-regularized latent space, in which the latent features of ECG follow a regular distribution and present smaller morphology variations than in the raw data space. Finally, a transfer learning framework is proposed to transfer the knowledge learned on ICDIRS to smaller datasets. On ICDIRS, ECGVEDNET achieves accuracy of 86.28%/88.31% within 5/10 ms tolerance for QRS onset and accuracy of 89.94%/91.16% within 5/10 ms tolerance for T peak. On QTDB, the average time errors computed for QRS onset and T peak are -1.86 ± 8.02 ms and -0.50 ± 12.96 ms, respectively, achieving state-of-the-art performances on both large and small-scale datasets. We will release the source code and the pre-trained model on ICDIRS once accepted.
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	160429-6
ISSN	1558-2531 ; 0018-9294
ISSN (online)	1558-2531
ISSN	0018-9294
DOI	10.1109/TBME.2024.3363077
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Article: A Brief Introduction to Some Aspects of the Fluid-Mosaic Model of Cell Membrane Structure and Its Importance in Membrane Lipid Replacement.

Nicolson, Garth L / Ferreira de Mattos, Gonzalo

Membranes

2021 Volume 11, Issue 12

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. ... ...

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, 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.
Language	English
Publishing date	2021-11-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2614641-1
ISSN	2077-0375
ISSN	2077-0375
DOI	10.3390/membranes11120947
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Article: The Fluid-Mosaic Model of Membrane Structure: still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years.

Nicolson, Garth L

Biochimica et biophysica acta

2014 Volume 1838, Issue 6, Page(s) 1451–1466

Abstract: ... mobility within the membrane matrix [S. J. Singer and G. L. Nicolson, Science 175 (1972) 720-731]. After ...

Abstract	In 1972 the Fluid-Mosaic Membrane Model of membrane structure was proposed based on thermodynamic principals of organization of membrane lipids and proteins and available evidence of asymmetry and lateral mobility within the membrane matrix [S. J. Singer and G. L. Nicolson, Science 175 (1972) 720-731]. After over 40years, this basic model of the cell membrane remains relevant for describing the basic nano-structures of a variety of intracellular and cellular membranes of plant and animal cells and lower forms of life. In the intervening years, however, new information has documented the importance and roles of specialized membrane domains, such as lipid rafts and protein/glycoprotein complexes, in describing the macrostructure, dynamics and functions of cellular membranes as well as the roles of membrane-associated cytoskeletal fences and extracellular matrix structures in limiting the lateral diffusion and range of motion of membrane components. These newer data build on the foundation of the original model and add new layers of complexity and hierarchy, but the concepts described in the original model are still applicable today. In updated versions of the model more emphasis has been placed on the mosaic nature of the macrostructure of cellular membranes where many protein and lipid components are limited in their rotational and lateral motilities in the membrane plane, especially in their natural states where lipid-lipid, protein-protein and lipid-protein interactions as well as cell-matrix, cell-cell and intracellular membrane-associated protein and cytoskeletal interactions are important in restraining the lateral motility and range of motion of particular membrane components. The formation of specialized membrane domains and the presence of tightly packed integral membrane protein complexes due to membrane-associated fences, fenceposts and other structures are considered very important in describing membrane dynamics and architecture. These structures along with membrane-associated cytoskeletal and extracellular structures maintain the long-range, non-random mosaic macro-organization of membranes, while smaller membrane nano- and submicro-sized domains, such as lipid rafts and protein complexes, are important in maintaining specialized membrane structures that are in cooperative dynamic flux in a crowded membrane plane. This Article is Part of a Special Issue Entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
MeSH term(s)	Animals ; Cell Membrane Structures/chemistry ; Cell Physiological Phenomena ; Humans ; Membrane Fluidity/physiology ; Membrane Lipids/chemistry ; Membrane Lipids/metabolism ; Membrane Microdomains/chemistry ; Membrane Microdomains/metabolism ; Membrane Proteins/chemistry ; Membrane Proteins/metabolism ; Models, Biological
Chemical Substances	Membrane Lipids ; Membrane Proteins
Language	English
Publishing date	2014-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamem.2013.10.019
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Article: Difference in topology of normal and tumour cell membranes shown by different surface distributions of ferritin-conjugated concanavalin A.

Nicolson, G L

Nature: New biology

2010 Volume 233, Issue 42, Page(s) 244–246

MeSH term(s)	3T3 Cells ; Animals ; Binding Sites ; Cell Membrane/metabolism ; Cell Transformation, Neoplastic ; Concanavalin A/biosynthesis ; Concanavalin A/chemistry ; Ferritins/biosynthesis ; Ferritins/chemistry ; Mice ; Mice, Inbred BALB C ; Neoplasms/chemistry ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Plant Lectins/chemistry ; Protein Binding
Chemical Substances	Plant Lectins ; ferritin-concanavalin A conjugate ; Concanavalin A (11028-71-0) ; Ferritins (9007-73-2)
Language	English
Publishing date	2010-05-17
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	120715-5
ISSN	0090-0028 ; 0369-4887
ISSN	0090-0028 ; 0369-4887
DOI	10.1038/newbio233244a0
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Article ; Online: Membrane Lipid Replacement with Glycerolphospholipids Slowly Reduces Self-Reported Symptom Severities in Chemically Exposed Gulf War Veterans

Garth L. Nicolson / Paul C. Breeding

International Journal of Translational Medicine, Vol 2, Iss 14, Pp 164-

2022 Volume 173

Abstract: ... diagnosed with Gulf War Illnesses (GWI) were utilized. These subjects took 6 g per day oral ...

Abstract	Background: Chemically exposed veterans of the 1991 Gulf War have few options for treatment of conditions and symptoms related to their chemical exposures. Membrane Lipid Replacement (MLR) with oral membrane glycerolphospholipids is a safe and effective method for slowly removing hydrophobic organic molecules from tissues, while enhancing mitochondrial function and decreasing the severity of certain signs and symptoms associated with multi-symptom illnesses. Methods: A preliminary open-label study utilizing 20 male veterans who were deployed to combat areas, exposed to environmental toxic chemicals and subsequently diagnosed with Gulf War Illnesses (GWI) were utilized. These subjects took 6 g per day oral glycerolphospholipids for 6 months, and the severities of over 100 signs and symptoms were self-reported at various times using illness survey forms. Results: In the sixteen patients that fully complied and completed the study, there were gradual and significant reductions of symptom severities in categories related to fatigue, pain, musculoskeletal, nasopharyngeal, breathing, vision, sleep, balance, and urinary, gastrointestinal and chemical sensitivities. There were no adverse incidents during the study, and the all-natural oral study supplement was extremely well tolerated. Conclusions: MLR with oral glycerolphospholipids appears to be a simple, safe and potentially effective method of slowly reducing the severities of multiple symptoms in chemically exposed veterans.
Keywords	chemical exposures ; multi-symptom illnesses ; Gulf War veterans ; Gulf War Illnesses ; membrane lipid supplements ; detoxification ; Computer applications to medicine. Medical informatics ; R858-859.7
Subject code	150
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analysis of preplatelets and their barbell platelet derivatives by imaging flow cytometry.

Kemble, Samuel / Dalby, Amanda / Lowe, Gillian C / Nicolson, Phillip L R / Watson, Steve P / Senis, Yotis / Thomas, Steven G / Harrison, Paul

Blood advances

2022 Volume 6, Issue 9, Page(s) 2932–2946

Abstract: Circulating large "preplatelets" undergo fission via barbell platelet intermediates into two smaller, mature platelets. In this study, we determine whether preplatelets and/or barbells are equivalent to reticulated/immature platelets by using ImageStream ...

Abstract	Circulating large "preplatelets" undergo fission via barbell platelet intermediates into two smaller, mature platelets. In this study, we determine whether preplatelets and/or barbells are equivalent to reticulated/immature platelets by using ImageStream flow cytometry and super-resolution microscopy. Immature platelets, preplatelets, and barbells were quantified in healthy and thrombocytopenic mice, healthy human volunteers, and patients with immune thrombocytopenia or undergoing chemotherapy. Preplatelets and barbells were 1.9% ± 0.18%/1.7% ± 0.48% (n = 6) and 3.3% ± 1.6%/0.5% ± 0.27% (n = 12) of total platelet counts in murine and human whole blood, respectively. Both preplatelets and barbells exhibited high expression of major histocompatibility complex class I with high thiazole orange and Mitotracker fluorescence. Tracking dye experiments confirmed that preplatelets transform into barbells and undergo fission ex vivo to increase platelet counts, with dependence on the cytoskeleton and normal mitochondrial respiration. Samples from antibody-induced thrombocytopenia in mice and patients with immune thrombocytopenia had increased levels of both preplatelets and barbells correlating with immature platelet levels. Furthermore, barbells were absent after chemotherapy in patients. In mice, in vivo biotinylation confirmed that barbells, but not all large platelets, were immature. This study demonstrates that a subpopulation of large platelets are immature preplatelets that can transform into barbells and undergo fission during maturation.
MeSH term(s)	Animals ; Blood Platelets ; Flow Cytometry/methods ; Humans ; Mice ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Thrombocytopenia
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021006073
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Article ; Online: Electroencephalography as a tool to predict cerebral oxygen metabolism during deep-hypothermic circulatory arrest in neonates with critical congenital heart disease.

Laurent, Gerard H / Ko, Tiffany S / Mensah-Brown, Kobina G / Mavroudis, Constantine D / Jacobwitz, Marin / Ranieri, Nicolina / Nicolson, Susan C / Gaynor, J William / Baker, Wesley B / Licht, Daniel J / Massey, Shavonne L / Lynch, Jennifer M

JTCVS open

2023 Volume 16, Page(s) 801–809

Abstract: Objectives: Recent research suggests that increased cerebral oxygen use during surgical intervention for neonates with congenital heart disease may play a role in the development of postoperative white matter injury. The objective of this study is to ... ...

Abstract	Objectives: Recent research suggests that increased cerebral oxygen use during surgical intervention for neonates with congenital heart disease may play a role in the development of postoperative white matter injury. The objective of this study is to determine whether increased cerebral electrical activity correlates with greater decrease of cerebral oxygen saturation during deep hypothermic circulatory arrest. Methods: Neonates with critical congenital heart disease requiring surgical intervention during the first week of life were studied. All subjects had continuous neuromonitoring with electroencephalography and an optical probe (to quantify cerebral oxygen saturation) during cardiac surgical repair that involved the use of cardiopulmonary bypass and deep hypothermic circulatory arrest. A simple linear regression was used to investigate the association between electroencephalography metrics before the deep hypothermic circulatory arrest period and the change in cerebral oxygen saturation during the deep hypothermic circulatory arrest period. Results: Sixteen neonates had both neuromonitoring modalities attached during surgical repair. Cerebral oxygen saturation data from 5 subjects were excluded due to poor data quality, yielding a total sample of 11 neonates. A simple linear regression model found that the presence of electroencephalography activity at the end of cooling is positively associated with the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest ( Conclusions: Electroencephalography characteristics within 5 minutes before the initiation of deep hypothermic circulatory arrest may be useful in predicting the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest. Electroencephalography may be an important tool for guiding cooling and the initiation of circulatory arrest to potentially decrease the prevalence of new white matter injury in neonates with critical congenital heart disease.
Language	English
Publishing date	2023-08-13
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-2736
ISSN (online)	2666-2736
DOI	10.1016/j.xjon.2023.08.004
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