The Role of Protein and Lipid Clustering in Lymphocyte Activation

Lamerton, Rachel E.; Lightfoot, Abbey; Nieves, Daniel J.; Owen, Dylan M.

doi:10.3389/fimmu.2021.600961

Cited by 18 publications

(18 citation statements)

References 70 publications

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“…The diameter of the cell was increased at the cell base if compared to higher stacks from E-1 to E-6, indicating cell flattening. The TAMRA-cap labeling on the rep-cells revealed granular structures in the membrane visible at the base (E-1) as well as on the upper part of the cells (E-5) evoked most probably due to the inherent clustering of membrane lipids and proteins …”

Section: Resultsmentioning

confidence: 99%

DNA Functionalized Spider Silk Nanohydrogels for Specific Cell Attachment and Patterning

et al. 2022

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Nucleated protein self-assembly of an azido modified spider silk protein was employed in the preparation of nanofibrillar networks with hydrogel-like properties immobilized on coatings of the same protein. Formation of the networks in a mild aqueous environment resulted in thicknesses between 2 and 60 nm, which were controlled only by the protein concentration. Incorporated azido groups in the protein were used to “click” short nucleic acid sequences onto the nanofibrils, which were accessible to specific hybridization-based modifications, as proved by fluorescently labeled DNA complements. A lipid modifier was used for efficient incorporation of DNA into the membrane of nonadherent Jurkat cells. Based on the complementarity of the nucleic acids, highly specific DNA-assisted immobilization of the cells on the nanohydrogels with tunable cell densities was possible. Addressability of the DNA cell-to-surface anchor was demonstrated with a competitive oligonucleotide probe, resulting in a rapid release of 75–95% of cells. In addition, we developed a photolithography-based patterning of arbitrarily shaped microwells, which served to spatially define the formation of the nanohydrogels. After detaching the photoresist and PEG-blocking of the surface, DNA-assisted immobilization of the Jurkat cells on the nanohydrogel microstructures was achieved with high fidelity.

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Section: Resultsmentioning

confidence: 99%

DNA Functionalized Spider Silk Nanohydrogels for Specific Cell Attachment and Patterning

et al. 2022

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“…It is plausible that cytokine modulation of key metabolic enzymes or energy usage by the immune system during acute infection are a major source of the metabolic changes associated with COVID-19 progression 61 . It has been shown for COVID-19 specifically that in T-cells cholesterol interacts with sphingolipids in membrane rafts in a manner that is dependent on the saturation state of the fatty acids 29 , and more generally that lipid raft formation has a crucial role in the cytotoxic activity of CD8 T-cells [62][63][64] . The increase in triglyceride composition of lipoprotein particles and their saturation state we observed with increased disease severity could result in altered immune function.…”

Section: Discussionmentioning

confidence: 99%

Metabolic and immune markers for precise monitoring of COVID-19 severity and treatment

Rendeiro

Vorkas

Krumsiek

et al. 2021

Preprint

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Deep understanding of the SARS-CoV-2 effects on host molecular pathways is paramount for the discovery of early biomarkers of outcome of coronavirus disease 2019 (COVID-19) and the identification of novel therapeutic targets. In that light, we generated metabolomic data from COVID-19 patient blood using high-throughput targeted nuclear magnetic resonance (NMR) spectroscopy and high-dimensional flow cytometry. We find considerable changes in serum metabolome composition of COVID-19 patients associated with disease severity, and response to tocilizumab treatment. We built a clinically annotated, biologically-interpretable space for precise time-resolved disease monitoring and characterize the temporal dynamics of metabolomic change along the clinical course of COVID-19 patients and in response to therapy. Finally, we leverage joint immuno-metabolic measurements to provide a novel approach for patient stratification and early prediction of severe disease. Our results show that high-dimensional metabolomic and joint immune-metabolic readouts provide rich information content for elucidation of the host response to infection and empower discovery of novel metabolic-driven therapies, as well as precise and efficient clinical action.

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“…In total, 249 measures were produced with 148 in absolute molar quantification. This platform (same metabolite measurements) has been extensively described and validated across large cohorts ( 68 , 69 ).…”

Section: Methodsmentioning

confidence: 99%

Metabolic and Immune Markers for Precise Monitoring of COVID-19 Severity and Treatment

et al. 2022

View full text Add to dashboard Cite

Deep understanding of the SARS-CoV-2 effects on host molecular pathways is paramount for the discovery of early biomarkers of outcome of coronavirus disease 2019 (COVID-19) and the identification of novel therapeutic targets. In that light, we generated metabolomic data from COVID-19 patient blood using high-throughput targeted nuclear magnetic resonance (NMR) spectroscopy and high-dimensional flow cytometry. We find considerable changes in serum metabolome composition of COVID-19 patients associated with disease severity, and response to tocilizumab treatment. We built a clinically annotated, biologically-interpretable space for precise time-resolved disease monitoring and characterize the temporal dynamics of metabolomic change along the clinical course of COVID-19 patients and in response to therapy. Finally, we leverage joint immuno-metabolic measurements to provide a novel approach for patient stratification and early prediction of severe disease. Our results show that high-dimensional metabolomic and joint immune-metabolic readouts provide rich information content for elucidation of the host’s response to infection and empower discovery of novel metabolic-driven therapies, as well as precise and efficient clinical action.

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The Role of Protein and Lipid Clustering in Lymphocyte Activation

Cited by 18 publications

References 70 publications

DNA Functionalized Spider Silk Nanohydrogels for Specific Cell Attachment and Patterning

DNA Functionalized Spider Silk Nanohydrogels for Specific Cell Attachment and Patterning

Metabolic and immune markers for precise monitoring of COVID-19 severity and treatment

Metabolic and Immune Markers for Precise Monitoring of COVID-19 Severity and Treatment

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