scholarly journals Phenotyping Polarization Dynamics Of Immune Cells Using A Lipid Droplet - Cell Pairing Microfluidic Platform

2021 ◽  
Author(s):  
L&eacutea Pinon ◽  
Nicolas Ruyssen ◽  
Judith Pineau ◽  
Olivier Mesdjian ◽  
Damien Cuverlier ◽  
...  
Keyword(s):  
Immune Cells ◽  
Lipid Droplets ◽  
Experimental System ◽  
Antigen Concentration ◽  
Immune Synapse ◽  
Tight Contact ◽  
Substrate Rigidity ◽  
Cognate Antigen ◽  
A Cell ◽  
Cellular Components

The immune synapse is the tight contact zone between a lymphocyte and a cell presenting its cognate antigen. This structure serves as a signaling platform and entails a polarization of intra-cellular components, necessary to the immunological function of the cell. While the surface properties of the presenting cell are known to control the formation of the synapse, their impact on polarization has not yet been studied. Using functional lipid droplets as tunable artificial presenting cells combined with a microfluidic pairing device, we simultaneously observe synchronized synapses and dynamically quantify polarization patterns of individual B cells. By assessing how the ligand concentration, the surface fluidity and the substrate rigidity impact this polarization, we show that its onset depends on the antigen concentration at the synapse, and that the substrate rigidity controls both its onset and its kinetics. Our experimental system enables a fine phenotyping of monoclonal cell populations based on their synaptic readout.

scholarly journals The dynamic behavior of lipid droplets in the pre-metastatic niche

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chunliang Shang ◽  
Jie Qiao ◽  
Hongyan Guo
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Stromal Cells ◽  
Lipid Droplets ◽  
Metastatic Tumor ◽  
Current Evidence ◽  
Biological Functions ◽  
Metastatic Niche ◽  
Niche Formation

AbstractThe pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.

scholarly journals CellNetVis: a web tool for visualization of biological networks using force-directed layout constrained by cellular components

2017 ◽  
Author(s):  
Henry Heberle ◽  
Marcelo Falsarella Carazzolle ◽  
Guilherme P. Telles ◽  
Gabriela Vaz Meirelles ◽  
Rosane Minghim
Keyword(s):  
Biological Networks ◽  
Visual Exploration ◽  
Web Tool ◽  
Biomolecular Interaction ◽  
Dense Networks ◽  
A Cell ◽  
Visualization Of Data ◽  
Cellular Compartments ◽  
Cellular Components ◽  
Dynamic Investigation

AbstractBackgroundThe advent of “omics” science has brought new perspectives in contemporary biology through the high-throughput analyses of molecular interactions, providing new clues in protein/gene function and in the organization of biological pathways. Biomolecular interaction networks, or graphs, are simple abstract representations where the components of a cell (e.g. proteins, metabolites etc.) are represented by nodes and their interactions are represented by edges. An appropriate visualization of data is crucial for understanding such networks, since pathways are related to functions that occur in specific regions of the cell. The force-directed layout is an important and widely used technique to draw networks according to their topologies. Placing the networks into cellular compartments helps to quickly identify where network elements are located and, more specifically, concentrated. Currently, only a few tools provide the capability of visually organizing networks by cellular compartments. Most of them cannot handle large and dense networks. Even for small networks with hundreds of nodes the available tools are not able to reposition the network while the user is interacting, limiting the visual exploration capability.ResultsHere we propose CellNetVis, a web tool to easily display biological networks in a cell diagram employing a constrained force-directed layout algorithm. The tool is freely available and open-source. It was originally designed for networks generated by the Integrated Interactome System and can be used with networks from others databases, like InnateDB.ConclusionsCellNetVis has demonstrated to be applicable for dynamic investigation of complex networks over a consistent representation of a cell on the Web, with capabilities not matched elsewhere.

scholarly journals A Decade of Mighty Lipophagy: What We Know and What Facts We Need to Know?

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Muhammad Babar Khawar ◽  
Muddasir Hassan Abbasi ◽  
Mussarat Rafiq ◽  
Naila Naz ◽  
Rabia Mehmood ◽  
...  
Keyword(s):  
Cell Death ◽  
Lipid Droplets ◽  
Lysosomal Enzymes ◽  
Lipid Homeostasis ◽  
Cellular Lipid ◽  
Biological Functions ◽  
Lysosomal Function ◽  
Selective Autophagy ◽  
Cellular Components ◽  
Different Levels

Lipids are integral cellular components that act as substrates for energy provision, signaling molecules, and essential constituents of biological membranes along with a variety of other biological functions. Despite their significance, lipid accumulation may result in lipotoxicity, impair autophagy, and lysosomal function that may lead to certain diseases and metabolic syndromes like obesity and even cell death. Therefore, these lipids are continuously recycled and redistributed by the process of selective autophagy specifically termed as lipophagy. This selective form of autophagy employs lysosomes for the maintenance of cellular lipid homeostasis. In this review, we have reviewed the current literature about how lipid droplets (LDs) are recruited towards lysosomes, cross-talk between a variety of autophagy receptors present on LD surface and lysosomes, and lipid hydrolysis by lysosomal enzymes. In addition to it, we have tried to answer most of the possible questions related to lipophagy regulation at different levels. Moreover, in the last part of this review, we have discussed some of the pathological states due to the accumulation of these LDs and their possible treatments under the light of currently available findings.

scholarly journals Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Science ◽  
2019 ◽  
Vol 365 (6460) ◽  
pp. eaav7188 ◽  
Author(s):  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Expression Profiles ◽  
Human Microglia ◽  
Histocompatibility Complex ◽  
The Central Nervous System ◽  
Reference Map ◽  
Peripheral Immune Cells ◽  
Genomic Map ◽  
Cellular Components

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

scholarly journals Mesenchymal Stromal-Like Cells in the Glioma Microenvironment: What Are These Cells?

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2628
Author(s):  
Anne Clavreul ◽  
Philippe Menei
Keyword(s):  
Blood Vessels ◽  
Immune Cells ◽  
Stromal Cells ◽  
Low Ph ◽  
Cancer Associated Fibroblasts ◽  
Tumor Resistance ◽  
Interstitial Pressure ◽  
Close Proximity ◽  
Cellular Components ◽  
Glioma Microenvironment

The glioma microenvironment is a critical regulator of tumor progression. It contains different cellular components such as blood vessels, immune cells, and neuroglial cells. It also contains non-cellular components, such as the extracellular matrix, extracellular vesicles, and cytokines, and has certain physicochemical properties, such as low pH, hypoxia, elevated interstitial pressure, and impaired perfusion. This review focuses on a particular type of cells recently identified in the glioma microenvironment: glioma-associated stromal cells (GASCs). This is just one of a number of names given to these mesenchymal stromal-like cells, which have phenotypic and functional properties similar to those of mesenchymal stem cells and cancer-associated fibroblasts. Their close proximity to blood vessels may provide a permissive environment, facilitating angiogenesis, invasion, and tumor growth. Additional studies are required to characterize these cells further and to analyze their role in tumor resistance and recurrence.

scholarly journals Dual binding motifs underpin the hierarchical association of perilipins1–3 with lipid droplets

2019 ◽  
Vol 30 (5) ◽  
pp. 703-716 ◽  
Author(s):  
Dalila Ajjaji ◽  
Kalthoum Ben M'barek ◽  
Michael L. Mimmack ◽  
Cheryl England ◽  
Haya Herscovitz ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Tissue Type ◽  
Binding Motifs ◽  
Amino Terminal ◽  
A Cell ◽  
Oil Water ◽  
Carboxy Terminal ◽  
Hierarchical Manner

Lipid droplets (LDs) in all eukaryotic cells are coated with at least one of the perilipin (Plin) family of proteins. They all regulate key intracellular lipases but do so to significantly different extents. Where more than one Plin is expressed in a cell, they associate with LDs in a hierarchical manner. In vivo, this means that lipid flux control in a particular cell or tissue type is heavily influenced by the specific Plins present on its LDs. Despite their early discovery, exactly how Plins target LDs and why they displace each other in a “hierarchical” manner remains unclear. They all share an amino-terminal 11-mer repeat (11mr) amphipathic region suggested to be involved in LD targeting. Here, we show that, in vivo, this domain functions as a primary highly reversible LD targeting motif in Plin1–3, and, in vitro, we document reversible and competitive binding between a wild-type purified Plin1 11mr peptide and a mutant with reduced binding affinity to both “naked” and phospholipid-coated oil–water interfaces. We also present data suggesting that a second carboxy-terminal 4-helix bundle domain stabilizes LD binding in Plin1 more effectively than in Plin2, whereas it weakens binding in Plin3. These findings suggest that dual amphipathic helical regions mediate LD targeting and underpin the hierarchical binding of Plin1–3 to LDs.

Pharmacotherapeuetic Options for the Treatment of Multiple Sclerosis

2012 ◽  
Vol 4 ◽  
pp. CMT.S8661 ◽  
Author(s):  
Alan M. Palmer
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cells ◽  
Cell Adhesion Molecule ◽  
Major Change ◽  
Clinical Development ◽  
Immunomodulatory Drugs ◽  
Amino Acid Peptide ◽  
A Cell ◽  
Patent Life ◽  
Neuro Inflammation

Multiple sclerosis is the most common progressive and disabling neurological condition in young adults. Neuro-inflammation is an early and persistent change and forms the basis of most pharmacotherapy for this disease. Immunomodulatory drugs are mainly biologies (β-interferons, a four amino acid peptide, and a monoclonal antibody to a cell adhesion molecule on the blood-CNS barrier) that either attenuate the inflammatory response or block the movement of immune cells into the CNS. They reduce the rate of relapse, but have little or no effect on the progression of disability. The market landscape for MS drugs is in the midst of major change because the patent life of many of these medicines will soon expire, which will lead to the emergence of biosimilars. In addition, new small molecule immunomodulatory and palliative drugs have entered the market, with more in the pipeline; a number of monoclonal antibodies and other immunomodulatory drugs are also in clinical development.

scholarly journals Mutations in the Lipopolysaccharide Biosynthesis Pathway Interfere with Crescentin-Mediated Cell Curvature in Caulobacter crescentus

2010 ◽  
Vol 192 (13) ◽  
pp. 3368-3378 ◽  
Author(s):  
Matthew T. Cabeen ◽  
Michelle A. Murolo ◽  
Ariane Briegel ◽  
N. Khai Bui ◽  
Waldemar Vollmer ◽  
...  
Keyword(s):  
Cell Wall ◽  
Caulobacter Crescentus ◽  
Cell Envelope ◽  
Cellular Systems ◽  
Biosynthesis Pathway ◽  
Cell Morphogenesis ◽  
Division Site ◽  
Growth Properties ◽  
A Cell ◽  
Cellular Components

ABSTRACT Bacterial cell morphogenesis requires coordination among multiple cellular systems, including the bacterial cytoskeleton and the cell wall. In the vibrioid bacterium Caulobacter crescentus, the intermediate filament-like protein crescentin forms a cell envelope-associated cytoskeletal structure that controls cell wall growth to generate cell curvature. We undertook a genetic screen to find other cellular components important for cell curvature. Here we report that deletion of a gene (wbqL) involved in the lipopolysaccharide (LPS) biosynthesis pathway abolishes cell curvature. Loss of WbqL function leads to the accumulation of an aberrant O-polysaccharide species and to the release of the S layer in the culture medium. Epistasis and microscopy experiments show that neither S-layer nor O-polysaccharide production is required for curved cell morphology per se but that production of the altered O-polysaccharide species abolishes cell curvature by apparently interfering with the ability of the crescentin structure to associate with the cell envelope. Our data suggest that perturbations in a cellular pathway that is itself fully dispensable for cell curvature can cause a disruption of cell morphogenesis, highlighting the delicate harmony among unrelated cellular systems. Using the wbqL mutant, we also show that the normal assembly and growth properties of the crescentin structure are independent of its association with the cell envelope. However, this envelope association is important for facilitating the local disruption of the stable crescentin structure at the division site during cytokinesis.

scholarly journals Receptor-mediated cell mechanosensing

2017 ◽  
Vol 28 (23) ◽  
pp. 3134-3155 ◽  
Author(s):  
Yunfeng Chen ◽  
Lining Ju ◽  
Muaz Rushdi ◽  
Chenghao Ge ◽  
Cheng Zhu
Keyword(s):  
Cell Receptor ◽  
Platelet Glycoprotein ◽  
Surface Receptors ◽  
Binding Interface ◽  
Substrate Rigidity ◽  
Step Model ◽  
Multistep Process ◽  
A Cell ◽  
Biochemical Signals ◽  
Cell Mechanosensing

Mechanosensing describes the ability of a cell to sense mechanical cues of its microenvironment, including not only all components of force, stress, and strain but also substrate rigidity, topology, and adhesiveness. This ability is crucial for the cell to respond to the surrounding mechanical cues and adapt to the changing environment. Examples of responses and adaptation include (de)activation, proliferation/apoptosis, and (de)differentiation. Receptor-mediated cell mechanosensing is a multistep process that is initiated by binding of cell surface receptors to their ligands on the extracellular matrix or the surface of adjacent cells. Mechanical cues are presented by the ligand and received by the receptor at the binding interface; but their transmission over space and time and their conversion into biochemical signals may involve other domains and additional molecules. In this review, a four-step model is described for the receptor-mediated cell mechanosensing process. Platelet glycoprotein Ib, T-cell receptor, and integrins are used as examples to illustrate the key concepts and players in this process.

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