Single Molecule Analysis of Integrin-ligand Interactions PDF Download
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Author: Chenyu Wu
Publisher:
ISBN: 9781339839424
Category :
Languages : en
Pages : 127
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Book Description
In conclusion, this work provided new insights into the kinetic mechanism of integrin-mediated leukocyte rolling and firm adhesion, but also a mechanism for lymphocyte homing through the unique ligand-specific regulation of integrin adhesion by different chemokines. Our findings are also fundamental to understanding integrin-GPCR transactivation, and Hantavirus pathogenesis.
Author: Chenyu Wu
Publisher:
ISBN: 9781339839424
Category :
Languages : en
Pages : 127
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Book Description
In conclusion, this work provided new insights into the kinetic mechanism of integrin-mediated leukocyte rolling and firm adhesion, but also a mechanism for lymphocyte homing through the unique ligand-specific regulation of integrin adhesion by different chemokines. Our findings are also fundamental to understanding integrin-GPCR transactivation, and Hantavirus pathogenesis.
Author: Johannes A. Elbe
Publisher: Springer Science & Business Media
ISBN: 1475740646
Category : Science
Languages : en
Pages : 277
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Book Description
Author: Johannes A. Eble
Publisher:
ISBN: 9781570594298
Category : Integrins
Languages : en
Pages : 273
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Book Description
Author: Alberto Sosa Costa
Publisher:
ISBN:
Category :
Languages : en
Pages : 155
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Book Description
The migration of leukocytes from the blood stream to sites of injury and infection in the extravascular tissues is fundamental for the immune response. Two of the main receptors mediating this process are the integrins aLß2 and a4ß1, both expressed on the leukocyte cell membrane, which bind to their respective ligands ICAM-1 and VCAM-1, expressed on endothelial cell (EC) membrane. The dynamic and lateral organization of integrins on the cell membrane has been shown to be crucial in the regulation of cell adhesion. Likewise, organization of ligands in small domains (clusters) would probably reinforce the bonds formed with the integrins, thus increasing leukocyte adhesion. However, how the spatiotemporal behavior of integrins and their ligands is affected by the influence of external factors, such as mechanical and/or biochemical stimuli, has not been extensively studied. In addition, the impact of such spatiotemporal changes in the process of leukocyte adhesion and migration has not been addressed yet. The main aim of this thesis has been to address these questions using a combination of state-of-art biophysical tools, including advanced cell imaging, single molecule dynamic approaches, cell mechanical stimulation, and custom-designed algorithms for data quantification. From the technical side, our general approach involved the use of single particle tracking (SPT) approaches to monitor the dynamics of individual molecules implicated in the process of the cell adhesion, in combination with different super-resolution microscopy techniques, such as STED and STORM, to visualize changes in their nanoscale organization upon the influence of biochemical and/or mechanical stimuli. To mechanically stimulate cells we developed two different approaches; namely, a mechanical stretching device and a parallel-plate flow chamber (PPFC). We integrated these devices into our single molecule set-up and succeeded in recording the diffusion of integrins on cells plated on the mechanical stretching device upon varying stress conditions. As part of this thesis, we also applied different custom-made data analysis algorithms existent in the Lab and developed novel algorithms aimed at tracking and quantifying changes in the migratory behavior of T-cells on ECs exposed to shear stress. Using this powerful palette of tools we discovered that, as a consequence of prolonged shear flow exposure, ICAM-1 undergoes a global reorganization on the EC membrane accompanied by the formation of ICAM-1 nanoclusters. These nanoclusters were found to co-localize with shear flow-induced actin-enriched patch-like structures. Moreover, we showed that T-cells migrate faster and interact for shorter period of times on ECs mechanically stimulated as compared to ECs not subjected to shear stimulation. Hence, from these results, we concluded that continuous shear flow regulates the spatial organization of cell adhesion receptors on ECs, which in turn modulates leukocyte migration. In addition, we showed that chemokine (CXCL12) stimulation leads to rapid and transient activation of the a4ß1 expressed on T cells. These changes in activation profile directly correlate with talin recruitment, restricted lateral diffusion and integrin immobilization. Moreover, co-stimulation with CXCL12 and the ligand VCAM-1 potentiated integrin immobilization. In addition, superresolution imaging revealed that the nanoscale organization of a4ß1 remains unaffected upon CXCL12 and/or VCAM-1 stimulation. Our data, thus, indicate that docking by talin of the chemokine-activated a4ß1 to the actin cytoskeleton favors integrin immobilization, which likely facilitates ligand interaction and increased adhesiveness. The overall finding of this thesis indicates that cells of the immune system respond to mechanical and biochemical stimuli by rapidly readjusting the spatiotemporal behavior of integrins and ligands on the cell membrane modulating in turn cell adhesion and migration.
Author: Miguel Vicente-Manzanares
Publisher: Humana
ISBN: 9781071609613
Category : Science
Languages : en
Pages : 315
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Book Description
This volume provides the most cutting edge technologies related to the study of integrin activation and the characterization of their vast interactomes. Chapters detail protocols on experimental approached to quantify focal adhesion parameters, integrin activation, and the lateral interaction of integrins with transmembrane binding partners. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, The Integrin Interactome: Methods and Protocols aims to give the reader a multi-scale journey from single bonds inside protein structures to the function of these crucial adhesion receptors at a whole organism level in physiology and pathology.
Author: Peter Hinterdorfer
Publisher: Springer Science & Business Media
ISBN: 0387764976
Category : Science
Languages : en
Pages : 634
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Book Description
This handbook describes experimental techniques to monitor and manipulate individual biomolecules, including fluorescence detection, atomic force microscopy, and optical and magnetic trapping. It includes single-molecule studies of physical properties of biomolecules such as folding, polymer physics of protein and DNA, enzymology and biochemistry, single molecules in the membrane, and single-molecule techniques in living cells.
Author: Michael R. King
Publisher: Elsevier
ISBN: 0080539637
Category : Science
Languages : en
Pages : 339
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Book Description
This comprehensive work discusses novel biomolecular surfaces that have been engineered to either control or measure cell function at the atomic, molecular, and cellular levels. Each chapter presents real results, concepts, and expert perspectives of how cells interact with biomolecular surfaces, with particular emphasis on interactions within complex mechanical environments such as in the cardiovascular system. In addition, the book provides detailed coverage of inflammation and cellular immune response as a useful model for how engineering concepts and tools may be effectively applied to complex systems in biomedicine. -Accessible to biologists looking for new ways to model their results and engineers interested in biomedical applications -Useful to researchers in biomaterials, inflammation, and vascular biology -Excellent resource for graduate students as a textbook in cell & tissue engineering or cell mechanics courses
Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
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Book Description
Author: Donald Gullberg
Publisher: Springer
ISBN: 9401791538
Category : Medical
Languages : en
Pages : 188
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Book Description
The integrin family is composed of 24 members and approximately ten years ago (2003) we published a book devoted to the nine I domain integrin subunits. In this second edition, I am pleased that most of the original authors have been able to contribute to the updated version. I domain containing integrins include collagen receptors and leukocyte receptors. In 2003 the knockout mouse phenotypes for all of the I domain integrins had not yet been published; they are now, and are summarized and discussed in this edition. Interestingly, a recent 10 integrin mutation in dogs has indicated that collagen-binding integrins in the musculoskeletal system might have much more severe phenotypes in larger animals/humans compared to the mild integrin phenotypes observed in collagen-binding integrin deficient mice. This finding is further discussed in the book. In the cancer field, the microenvironment is taking center stage, and here collagen receptors on fibroblasts are predicted to play important roles in paracrine signaling, in regulating tissue stiffness and matrix remodeling. New technologies, new mouse models in combination with analyses of I integrins in larger animals/humans are thus predicted to increase our knowledge about this group of receptors. With this in mind we look forward to another 10 years of research with I domain integrins.
Author: Donald Huddler
Publisher: John Wiley & Sons
ISBN: 111909948X
Category : Science
Languages : en
Pages : 148
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Book Description
Applied Biophysics for Drug Discovery is a guide to new techniques and approaches to identifying and characterizing small molecules in early drug discovery. Biophysical methods are reasserting their utility in drug discovery and through a combination of the rise of fragment-based drug discovery and an increased focus on more nuanced characterisation of small molecule binding, these methods are playing an increasing role in discovery campaigns. This text emphasizes practical considerations for selecting and deploying core biophysical method, including but not limited to ITC, SPR, and both ligand-detected and protein-detected NMR. Topics covered include: • Design considerations in biophysical-based lead screening • Thermodynamic characterization of protein-compound interactions • Characterizing targets and screening reagents with HDX-MS • Microscale thermophoresis methods (MST) • Screening with Weak Affinity Chromatography • Methods to assess compound residence time • 1D-NMR methods for hit identification • Protein-based NMR methods for SAR development • Industry case studies integrating multiple biophysical methods This text is ideal for academic investigators and industry scientists planning hit characterization campaigns or designing and optimizing screening strategies.
