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Cell May 2019Over the last several decades, an impressive array of advanced microscopic and analytical tools, such as single-particle tracking and nanoscopic fluorescence correlation... (Review)
Review
Over the last several decades, an impressive array of advanced microscopic and analytical tools, such as single-particle tracking and nanoscopic fluorescence correlation spectroscopy, has been applied to characterize the lateral organization and mobility of components in the plasma membrane. Such analysis can tell researchers about the local dynamic composition and structure of membranes and is important for predicting the outcome of membrane-based reactions. However, owing to the unresolved complexity of the membrane and the structures peripheral to it, identification of the detailed molecular origin of the interactions that regulate the organization and mobility of the membrane has not proceeded quickly. This Perspective presents an overview of how cell-surface structure may give rise to the types of lateral mobility that are observed and some potentially fruitful future directions to elucidate the architecture of these structures in more molecular detail.
Topics: Cell Membrane; Lipid Bilayers; Membrane Lipids; Membrane Microdomains; Membrane Proteins
PubMed: 31051105
DOI: 10.1016/j.cell.2019.04.018 -
Theranostics 2023Cancer is generally considered a result of genetic mutations that cause epigenetic changes, leading to anomalous cellular behavior. Since 1970s, an increasing... (Review)
Review
Cancer is generally considered a result of genetic mutations that cause epigenetic changes, leading to anomalous cellular behavior. Since 1970s, an increasing understanding of the plasma membrane and specifically the lipid alterations in tumor cells have provided novel insights for cancer therapy. Moreover, the advances in nanotechnology offer a potential opportunity to target the tumor plasma membrane while minimizing side effects on normal cells. To further develop membrane lipid perturbing tumor therapy, the first section of this review demonstrates the association between plasma membrane physicochemical properties and tumor signaling, metastasis, and drug resistance. The second section highlights existing nanotherapeutic strategies for membrane disruption, including lipid peroxide accumulation, cholesterol regulation, membrane structure disruption, lipid raft immobilization, and energy-mediated plasma membrane perturbation. Finally, the third section evaluates the prospects and challenges of plasma membrane lipid perturbing therapy as a therapeutic strategy for cancers. The reviewed membrane lipid perturbing tumor therapy strategies are expected to bring about necessary changes in tumor therapy in the coming decades.
Topics: Humans; Neoplasms; Membrane Lipids; Cell Membrane; Membrane Microdomains; Nanotechnology
PubMed: 37215569
DOI: 10.7150/thno.82189 -
Current Topics in Membranes 2015The lipid bilayer of the plasma membrane is thought to be compartmentalized by the presence of lipid-protein microdomains. In eukaryotic cells, microdomains composed of... (Review)
Review
The lipid bilayer of the plasma membrane is thought to be compartmentalized by the presence of lipid-protein microdomains. In eukaryotic cells, microdomains composed of sterols and sphingolipids, commonly known as lipid rafts, are believed to exist, and reports on the presence of sterol- or protein-mediated microdomains in bacterial cell membranes are also appearing. Despite increasing attention, little is known about microdomains in the plasma membrane of pathogenic microorganisms. This review attempts to provide an overview of the current state of knowledge of lipid rafts in pathogenic fungi and bacteria. The current literature on characterization of microdomains in pathogens is reviewed, and their potential role in growth, pathogenesis, and drug resistance is discussed. Better insight into the structure and function of membrane microdomains in pathogenic microorganisms might lead to a better understanding of their pathogenesis and development of raft-mediated approaches for therapy.
Topics: Animals; Bacteria; Bacterial Infections; Cholesterol; Drug Resistance; Fungi; Humans; Lipid Bilayers; Membrane Microdomains; Mycoses
PubMed: 26015285
DOI: 10.1016/bs.ctm.2015.03.005 -
Journal of Lipid Research May 2020Lipid rafts are organized plasma membrane microdomains, which provide a distinct level of regulation of cellular metabolism and response to extracellular stimuli,...
Lipid rafts are organized plasma membrane microdomains, which provide a distinct level of regulation of cellular metabolism and response to extracellular stimuli, affecting a diverse range of physiologic and pathologic processes. This Thematic Review Series focuses on Biology of Lipid Rafts rather than on their composition or structure. The aim is to provide an overview of ideas on how lipid rafts are involved in regulation of different pathways and how they interact with other layers of metabolic regulation. Articles in the series will review the involvement of lipid rafts in regulation of hematopoiesis, production of extracellular vesicles, host interaction with infection, and the development and progression of cancer, neuroinflammation, and neurodegeneration, as well as the current outlook on therapeutic targeting of lipid rafts.
Topics: Humans; Membrane Microdomains
PubMed: 31462515
DOI: 10.1194/jlr.IN119000330 -
International Journal of Molecular... Aug 2021Tetraspanins are a family of transmembrane proteins that form a network of protein-protein interactions within the plasma membrane. Within this network, tetraspanin are...
Tetraspanins are a family of transmembrane proteins that form a network of protein-protein interactions within the plasma membrane. Within this network, tetraspanin are thought to control the lateral segregation of their partners at the plasma membrane through mechanisms involving specific lipids. Here, we used a single molecule tracking approach to study the membrane behavior of tetraspanins in mammary epithelial cells and demonstrate that despite a common overall behavior, each tetraspanin (CD9, CD81 and CD82) has a specific signature in terms of dynamics. Furthermore, we demonstrated that tetraspanin dynamics on the cell surface are dependent on gangliosides. More specifically, we found that CD82 expression increases the dynamics of CD81 and alters its localization at the plasma membrane, this has no effect on the behavior of CD9. Our results provide new information on the ability of CD82 and gangliosides to differentially modulate the dynamics and organization of tetraspanins at the plasma membrane and highlight that its lipid and protein composition is involved in the dynamical architecture of the tetraspanin web. We predict that CD82 may act as a regulator of the lateral segregation of specific tetraspanins at the plasma membrane while gangliosides could play a crucial role in establishing tetraspanin-enriched areas.
Topics: Cell Membrane; Cells, Cultured; Epithelial Cells; Gangliosides; Humans; Kangai-1 Protein; Membrane Microdomains; Tetraspanin 28
PubMed: 34445169
DOI: 10.3390/ijms22168459 -
FEBS Letters May 2010Membranes with simple lipid composition exhibit complex phase behavior. Ordered and disordered liquid phases can coexist in cholesterol-containing membranes with lipid... (Review)
Review
Membranes with simple lipid composition exhibit complex phase behavior. Ordered and disordered liquid phases can coexist in cholesterol-containing membranes with lipid compositions resembling biological membranes and at physiological temperatures. Research during the last years suggests that these lipid domains play a role in the organization of biological membranes. Understanding the principles that govern the formation and stability of lipid domains is of great importance to build a model that properly describes membrane structure and function. In this review, we describe the current knowledge of the chemical and physical basis of lipid domains and its application to biological membranes.
Topics: Animals; Cell Membrane; Humans; Lipid Bilayers; Lipid Metabolism; Membrane Fluidity; Membrane Microdomains
PubMed: 20036662
DOI: 10.1016/j.febslet.2009.12.036 -
Cell Biology and Toxicology Oct 2017Infectious diseases pose major socioeconomic and health-related threats to millions of people across the globe. Strategies to combat infectious diseases derive from our... (Review)
Review
Infectious diseases pose major socioeconomic and health-related threats to millions of people across the globe. Strategies to combat infectious diseases derive from our understanding of the complex interactions between the host and specific bacterial, viral, and fungal pathogens. Lipid rafts are membrane microdomains that play important role in life cycle of microbes. Interaction of microbial pathogens with host membrane rafts influences not only their initial colonization but also their spread and the induction of inflammation. Therefore, intervention strategies aimed at modulating the assembly of membrane rafts and/or regulating raft-directed signaling pathways are attractive approaches for the. management of infectious diseases. The current review discusses the latest advances in terms of techniques used to study the role of membrane microdomains in various pathological conditions and provides updated information regarding the role of membrane rafts during bacterial, viral and fungal infections.
Topics: Animals; Bacterial Infections; Communicable Diseases; Humans; Membrane Microdomains; Signal Transduction; Virus Diseases
PubMed: 28275881
DOI: 10.1007/s10565-017-9386-9 -
FEBS Letters Aug 2014Membrane microdomains denoted commonly as lipid rafts (or membrane rafts) have been implicated in T-cell receptor (TCR), and more generally immunoreceptor, signaling for... (Review)
Review
Membrane microdomains denoted commonly as lipid rafts (or membrane rafts) have been implicated in T-cell receptor (TCR), and more generally immunoreceptor, signaling for over 25 years. However, this area of research has been complicated by doubts about the real nature (and even existence) of these membrane entities, especially because of methodological problems connected with possible detergent artefacts. Recent progress in biophysical approaches and functional studies of raft resident proteins apparently clarified many controversial aspects in this area. At present, the prevailing view is that these membrane microdomains are indeed involved in many aspects of cell biology, including immunoreceptor signaling. Moreover, several other types of raft-like microdomains (perhaps better termed nanodomains) have been described, which apparently also play important biological roles.
Topics: Animals; Humans; Membrane Microdomains; Receptors, Antigen, T-Cell; Signal Transduction
PubMed: 24911201
DOI: 10.1016/j.febslet.2014.05.047 -
Annual Review of Physical Chemistry Apr 2021Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support... (Review)
Review
Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support for the notion that lipid organization plays an important role in modulating this heterogeneity. Various biophysical mechanisms rooted in the concept of liquid-liquid phase separation have been proposed to explain diverse experimental observations of heterogeneity in model and cell membranes with distinct but overlapping applicability. In this review, we focus on the evidence for and the consequences of the hypothesis that the plasma membrane is poised near an equilibrium miscibility critical point. Critical phenomena explain certain features of the heterogeneity observed in cells and model systems but also go beyond heterogeneity to predict other interesting phenomena, including responses to perturbations in membrane composition.
Topics: Cell Membrane; Eukaryotic Cells; Membrane Lipids; Membrane Microdomains; Membrane Proteins
PubMed: 33710910
DOI: 10.1146/annurev-physchem-090419-115951 -
Biochimica Et Biophysica Acta Jun 2014This review deals with the effects of synthetic and natural fatty acids on the biophysical properties of membranes, and on their implication on cell function. Natural... (Review)
Review
This review deals with the effects of synthetic and natural fatty acids on the biophysical properties of membranes, and on their implication on cell function. Natural fatty acids are constituents of more complex lipids, like triacylglycerides or phospholipids, which are used by cells to store and obtain energy, as well as for structural purposes. Accordingly, natural and synthetic fatty acids may modify the structure of the lipid membrane, altering its microdomain organization and other physical properties, and provoking changes in cell signaling. Therefore, by modulating fatty acids it is possible to regulate the structure of the membrane, influencing the cell processes that are reliant on this structure and potentially reverting pathological cell dysfunctions that may provoke cancer, diabetes, hypertension, Alzheimer's and Parkinson's disease. The so-called Membrane Lipid Therapy offers a strategy to regulate the membrane composition through drug administration, potentially reverting pathological processes by re-adapting cell membrane structure. Certain fatty acids and their synthetic derivatives are described here that may potentially be used in such therapies, where the cell membrane itself can be considered as a target to combat disease. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.
Topics: Cell Membrane Structures; Cell Physiological Phenomena; Fatty Acids; Humans; Membrane Microdomains
PubMed: 24388951
DOI: 10.1016/j.bbamem.2013.12.021