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Cells Sep 2021Eukaryotic cells contain dynamic membrane-bound organelles that are constantly remodeled in response to physiological and environmental cues. Key organelles are the... (Review)
Review
Eukaryotic cells contain dynamic membrane-bound organelles that are constantly remodeled in response to physiological and environmental cues. Key organelles are the endoplasmic reticulum, the Golgi apparatus and the plasma membrane, which are interconnected by vesicular traffic through the secretory transport route. Numerous viruses, especially enveloped viruses, use and modify compartments of the secretory pathway to promote their replication, assembly and cell egression by hijacking the host cell machinery. In some cases, the subversion mechanism has been uncovered. In this review, we summarize our current understanding of how the secretory pathway is subverted and exploited by viruses belonging to , , and families.
Topics: Biological Transport; Cell Membrane; Endoplasmic Reticulum; Golgi Apparatus; Humans; Secretory Pathway; Viruses
PubMed: 34685515
DOI: 10.3390/cells10102535 -
Biochimica Et Biophysica Acta Apr 2015Ligand-receptor interactions, which represent the core for cell signaling and internalization processes are largely affected by the spatial configuration of host cell... (Review)
Review
Ligand-receptor interactions, which represent the core for cell signaling and internalization processes are largely affected by the spatial configuration of host cell receptors. There is a growing piece of evidence that receptors are not homogeneously distributed within the plasma membrane, but are rather pre-clustered in nanodomains, or clusters are formed upon ligand binding. Pathogens have evolved many strategies to evade the host immune system and to ensure their survival by hijacking plasma membrane receptors that are most often associated with lipid rafts. In this review, we discuss the early stage molecular and physiological events that occur following ligand binding to host cell glycolipids. The ability of various biological ligands (e.g. toxins, lectins, viruses or bacteria) that bind to glycolipids to induce their own uptake into mammalian cells by creating negative membrane curvature and membrane invaginations is explored. We highlight recent trends in understanding nanoscale plasma membrane (re-)organization and present the benefits of using synthetic membrane systems. This article is part of a Special Issue entitled: Nanoscale membrane organisation and signalling.
Topics: Animals; Bacteria; Cell Membrane; Endocytosis; Glycolipids; Glycoproteins; Humans; Ligands
PubMed: 25450969
DOI: 10.1016/j.bbamcr.2014.11.014 -
Acta Biochimica Et Biophysica Sinica Jul 2023Membraneless organelles (MLO) regulate diverse biological processes in a spatiotemporally controlled manner spanning from inside to outside of the cells. The plasma... (Review)
Review
Membraneless organelles (MLO) regulate diverse biological processes in a spatiotemporally controlled manner spanning from inside to outside of the cells. The plasma membrane (PM) at the cell surface serves as a central platform for forming multi-component signaling hubs that sense mechanical and chemical cues during physiological and pathological conditions. During signal transduction, the assembly and formation of membrane-bound MLO are dynamically tunable depending on the physicochemical properties of the surrounding environment and partitioning biomolecules. Biomechanical properties of MLO-associated membrane structures can control the microenvironment for biomolecular interactions and assembly. Lipid-protein complex interactions determine the catalytic region's assembly pattern and assembly rate and, thereby, the amplitude of activities. In this review, we will focus on how cell surface microenvironments, including membrane curvature, surface topology and tension, lipid-phase separation, and adhesion force, guide the assembly of PM-associated MLO for cell signal transductions.
Topics: Mechanotransduction, Cellular; Cell Membrane; Biomolecular Condensates; Cell Adhesion; Membrane Lipids; Animals
PubMed: 37475548
DOI: 10.3724/abbs.2023132 -
The Journal of Biological Chemistry Jul 2015Septins are GTP-binding proteins that form filaments and higher-order structures on the cell cortex of eukaryotic cells and associate with actin and microtubule... (Review)
Review
Septins are GTP-binding proteins that form filaments and higher-order structures on the cell cortex of eukaryotic cells and associate with actin and microtubule cytoskeletal networks. When assembled, septins coordinate cell division and contribute to cell polarity maintenance and membrane remodeling. These functions manifest themselves via scaffolding of cytosolic proteins and cytoskeletal networks to specific locations on membranes and by forming diffusional barriers that restrict lateral diffusion of proteins embedded in membranes. Notably, many neurodegenerative diseases and cancers have been characterized as having misregulated septins, suggesting that their functions are relevant to diverse diseases. Despite the importance of septins, little is known about what features of the plasma membrane influence septin recruitment and alternatively, how septins influence plasma membrane properties. Septins have been localized to the cell cortex at the base of cilia, the mother-bud neck of yeast, and branch points of filamentous fungi and dendritic spines, in cleavage furrows, and in retracting membrane protrusions in mammalian cells. These sites all possess some degree of curvature and are likely composed of distinct lipid pools. Depending on the context, septins may act alone or in concert with other cytoskeletal elements to influence and sense membrane properties. The degree to which septins react to and/or induce changes in shape and lipid composition are discussed here. As septins are an essential player in basic biology and disease, understanding the interplay between septins and the plasma membrane is critical and may yield new and unexpected functions.
Topics: Animals; Cell Cycle; Cell Division; Cell Membrane; Cell Polarity; Cell Shape; Cytoplasm; Humans; Models, Biological; Models, Molecular; Protein Multimerization; Septins
PubMed: 25957401
DOI: 10.1074/jbc.R114.634444 -
Journal of Extracellular Vesicles Sep 2021Plasma membrane curvature is an important factor in the regulation of cellular phenotype and is critical for various cellular activities including the shedding of... (Review)
Review
Plasma membrane curvature is an important factor in the regulation of cellular phenotype and is critical for various cellular activities including the shedding of extracellular vesicles (EV). One of the most striking morphological features of cells is different plasma membrane-covered extensions supported by actin core such as filopodia and microvilli. Despite the various functions of these extensions are partially unexplained, they are known to facilitate many crucial cellular functions such as migration, adhesion, absorption, and secretion. Due to the rapid increase in the research activity of EVs, there is raising evidence that one of the general features of cellular plasma membrane protrusions is to act as specialized platforms for the budding of EVs. This review will focus on early observations and recent findings supporting this hypothesis, discuss the putative budding and shedding mechanisms of protrusion-derived EVs and their biological significance.
Topics: Cell Membrane; Extracellular Vesicles; Humans; Microscopy, Electron, Scanning
PubMed: 34533887
DOI: 10.1002/jev2.12148 -
International Journal of Molecular... Jul 2020The cell membrane is a complex and highly regulated system that is composed of lipid bilayer and proteins. One of the main functions of the cell membrane is the... (Review)
Review
The cell membrane is a complex and highly regulated system that is composed of lipid bilayer and proteins. One of the main functions of the cell membrane is the regulation of cell entry. Cell-penetrating peptides (CPPs) are defined as peptides that can cross the plasma membrane and deliver their cargo inside the cell. The uptake of a peptide is determined by its sequence and biophysicochemical properties. At the same time, the uptake mechanism and efficiency are shown to be dependent on local peptide concentration, cell membrane lipid composition, characteristics of the cargo, and experimental methodology, suggesting that a highly efficient CPP in one system might not be as productive in another. To better understand the dependence of CPPs on the experimental system, we present a review of the in vitro assays that have been employed in the literature to evaluate CPPs and CPP-cargos. Our comprehensive review suggests that utilization of orthogonal assays will be more effective for deciphering the true ability of CPPs to translocate through the membrane and enter the cell cytoplasm.
Topics: Animals; Cell Membrane; Cell Membrane Permeability; Cell-Penetrating Peptides; Drug Delivery Systems; Endocytosis; Humans; Lipid Bilayers; Membrane Lipids; Protein Transport
PubMed: 32630650
DOI: 10.3390/ijms21134719 -
Proceedings of the National Academy of... Oct 2021Recent work has highlighted roles for thermodynamic phase behavior in diverse cellular processes. Proteins and nucleic acids can phase separate into three-dimensional...
Recent work has highlighted roles for thermodynamic phase behavior in diverse cellular processes. Proteins and nucleic acids can phase separate into three-dimensional liquid droplets in the cytoplasm and nucleus and the plasma membrane of animal cells appears tuned close to a two-dimensional liquid-liquid critical point. In some examples, cytoplasmic proteins aggregate at plasma membrane domains, forming structures such as the postsynaptic density and diverse signaling clusters. Here we examine the physics of these surface densities, employing minimal simulations of polymers prone to phase separation coupled to an Ising membrane surface in conjunction with a complementary Landau theory. We argue that these surface densities are a phase reminiscent of prewetting, in which a molecularly thin three-dimensional liquid forms on a usually solid surface. However, in surface densities the solid surface is replaced by a membrane with an independent propensity to phase separate. We show that proximity to criticality in the membrane dramatically increases the parameter regime in which a prewetting-like transition occurs, leading to a broad region where coexisting surface phases can form even when a bulk phase is unstable. Our simulations naturally exhibit three-surface phase coexistence even though both the membrane and the polymer bulk only display two-phase coexistence on their own. We argue that the physics of these surface densities may be shared with diverse functional structures seen in eukaryotic cells.
Topics: Animals; Cell Membrane; Cytoplasm; Polymers; Post-Synaptic Density; Proteins; Thermodynamics
PubMed: 34599097
DOI: 10.1073/pnas.2103401118 -
Nano Letters Aug 2023The bioengineering applications of cells, such as cell printing and multicellular assembly, are directly limited by cell damage and death due to a harsh environment....
The bioengineering applications of cells, such as cell printing and multicellular assembly, are directly limited by cell damage and death due to a harsh environment. Improved cellular robustness thus motivates investigations into cell encapsulation, which provides essential protection. Here we target the cell-surface glycocalyx and cross-link two layers of DNA nanorods on the cellular plasma membrane to form a modular and programmable nanoshell. We show that the DNA origami nanoshell modulates the biophysical properties of cell membranes by enhancing the membrane stiffness and lowering the lipid fluidity. The nanoshell also serves as armor to protect cells and improve their viability against mechanical stress from osmotic imbalance, centrifugal forces, and fluid shear stress. Moreover, it enables mediated cell-cell interactions for effective and robust multicellular assembly. Our results demonstrate the potential of the nanoshell, not only as a cellular protection strategy but also as a platform for cell and cell membrane manipulation.
Topics: Artificial Cells; Cell Membrane; Nanoshells; DNA; Nanostructures
PubMed: 37463308
DOI: 10.1021/acs.nanolett.3c01878 -
Protein Science : a Publication of the... Jun 2020Our understanding of the plasma membrane structure has undergone a major change since the proposal of the fluid mosaic model of Singer and Nicholson in the 1970s. In... (Review)
Review
Our understanding of the plasma membrane structure has undergone a major change since the proposal of the fluid mosaic model of Singer and Nicholson in the 1970s. In this model, the membrane, composed of over thousand lipid and protein species, is organized as a well-equilibrated two-dimensional fluid. Here, the distribution of lipids is largely expected to reflect a multicomponent system, and proteins are expected to be surrounded by an annulus of specialized lipid species. With the recognition that a multicomponent lipid membrane is capable of phase segregation, the membrane is expected to appear as patchwork quilt pattern of membrane domains. However, the constituents of a living membrane are far from being well equilibrated. The living cell membrane actively maintains a trans-bilayer asymmetry of composition, and its constituents are subject to a number of dynamic processes due to synthesis, lipid transfer as well as membrane traffic and turnover. Moreover, membrane constituents engage with the dynamic cytoskeleton of a living cell, and are both passively as well as actively manipulated by this engagement. The extracellular matrix and associated elements also interact with membrane proteins contributing to another layer of interaction. At the nano- and mesoscale, the organization of lipids and proteins emerge from these encounters, as well as from protein-protein, protein-lipid, and lipid-lipid interactions in the membrane. New methods to study the organization of membrane components at these scales have also been developed, and provide an opportunity to synthesize a new picture of the living cell surface as an active membrane composite.
Topics: Animals; Cell Membrane; Humans; Lipids; Membrane Lipids
PubMed: 32297381
DOI: 10.1002/pro.3874 -
Biochemical Society Transactions Oct 2022Continuous reshaping of the plasma membrane into pleomorphic shapes is critical for a plethora of cellular functions. How the cell carries out this enigmatic control of... (Review)
Review
Continuous reshaping of the plasma membrane into pleomorphic shapes is critical for a plethora of cellular functions. How the cell carries out this enigmatic control of membrane remodeling has remained an active research field for decades and several molecular and biophysical mechanisms have shown to be involved in overcoming the energy barrier associated with membrane bending. The reported mechanisms behind membrane bending have been largely concerned with structural protein features, however, in the last decade, reports on the ability of densely packed proteins to bend membranes by protein-protein crowding, have challenged prevailing mechanistic views. Crowding has now been shown to generate spontaneous vesicle formation and tubular morphologies on cell- and model membranes, demonstrating crowding as a relevant player involved in the bending of membranes. Still, current research is largely based on unnatural overexpression of proteins in non-native domains, and together with efforts in modeling, this has led to questioning the in vivo impact of crowding. In this review, we examine this previously overlooked mechanism by summarizing recent advances in the understanding of protein-protein crowding and its prevalence in cellular membrane-shaping processes.
Topics: Membrane Proteins; Cell Membrane; Biophysics; Endocytosis
PubMed: 36214373
DOI: 10.1042/BST20210883