<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Receptor-mediated Forces for Cell Sensing of Extracellular\r\nLigands and for Virus Particle Uptake"^^ . "Mechanical forces between cells ensure organic development and\r\nhomeostasis, but they are also associated with diseases such as cancer\r\nor viral infections. The absolute forces in nature can be as high as\r\n1.5 kN, which allows the mantis shrimp to smash oysters, down to a\r\nfew pN transduced by single cellular receptors. However, these small\r\nforces are strong enough for cells to probe their local environment.\r\nWhile the mechanism, which enables cells to investigate the stiffness\r\nof their surrounding, is already well elucidated, information on how\r\ncells sense spatial distribution of ligands is missing.\r\nIn this thesis I established a method, which allows to measure cellular\r\ntraction forces on elastic substrates with varying nano-spacing\r\nof extracellular ligands. In contrast to previous studies on stiff substrates,\r\nadhesion complexes and tractions were larger for longer distances\r\nbetween extracellular adhesion sites. This can be theoretically\r\nexplained by the force load on individual integrin receptors, which\r\nhas to exceed a certain threshold value to promote adhesion growth\r\nthrough conformational changes in a protein of the “clutch complex”.\r\nIn order to experimentally access the force load per integrin heterodimer,\r\nI combined molecular tension fluorescence microscopy\r\n(MTFM) with traction force microscopy (TFM). For the first time, I\r\ncould assess a homogeneous distribution of forces > 19pN underneath\r\nthe adhesion area of cells on soft substrates. Simultaneously,\r\nmacroscopic tractions up to 2.7 kPa were observed at the cell edges.\r\nApplying stronger tension probes and analyzing tractions in the zdirection\r\nwill help to cross-validate the results obtained from these\r\ntwo state-of-the-art methods in biomechanics as a next step.\r\nIn the second part I investigated the mechanical parameters of\r\nvirus particle uptake by cells. Many intracellular pathogens, such as\r\nmammalian reoviruses as employed in this thesis, mimic extracellular\r\nmotives to interact with host cells and initiate their internalization.\r\nThis leads to the assumption that host cells sense this specific ligand\r\npresentation, engage the endocytic machinery and generate forces,\r\nwhich are able to overcome the bending and tension energy of their\r\nplasma membrane.\r\nI demonstrated that these forces exerted on single reovirus particles\r\non the basolateral side of cells are strong enough to break down the\r\nbiotin-NeutrAvidin bond used for virus immobilization on stiff and\r\nsoft substrates. I quantified the forces to exceed 40pN by kinetic analysis\r\nof the tearing of viruses from these surfaces and single MTFM\r\nwith covalently immobilized reoviruses.\r\nThe herein presented methods are powerful tools to study forces exerted\r\nby individual receptors as well as on single particles e.g. during\r\nendocytosis. The involvement of the actin cytoskeleton, specific receptors\r\nor molecules of the endocytic machinery was examined. Inhibition\r\nof the ligand-receptor interactions between reoviruses and cells\r\ndid not significantly change the rate of virus uptake. Interestingly,\r\nbare nanoparticles of comparable diameter lacking specific binding\r\nsites were torn off at a similar rate and thus with the same forces\r\nas viruses. Hence, specific receptors seem to be dispensable for virus\r\nparticle uptake."^^ . "2019" . . . . . . . "Tina"^^ . "Wiegand"^^ . "Tina Wiegand"^^ . . . . . . "Receptor-mediated Forces for Cell Sensing of Extracellular\r\nLigands and for Virus Particle Uptake (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Receptor-mediated Forces for Cell Sensing of Extracellular\r\nLigands and for Virus Particle Uptake (PDF)"^^ . . . "Dissertation_TinaWiegand_FINAL_pdfa.pdf"^^ . . . "Receptor-mediated Forces for Cell Sensing of Extracellular\r\nLigands and for Virus Particle Uptake (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Receptor-mediated Forces for Cell Sensing of Extracellular\r\nLigands and for Virus Particle Uptake (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Receptor-mediated Forces for Cell Sensing of Extracellular\r\nLigands and for Virus Particle Uptake (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Receptor-mediated Forces for Cell Sensing of Extracellular\r\nLigands and for Virus Particle Uptake (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #24163 \n\nReceptor-mediated Forces for Cell Sensing of Extracellular \nLigands and for Virus Particle Uptake\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "540 Chemie"@de . "540 Chemistry and allied sciences"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . . . "600 Technik, Medizin, angewandte Wissenschaften"@de . "600 Technology (Applied sciences)"@en . .