https://www.burkhardtlab.org/home daily 1.0 2022-08-10 https://images.squarespace-cdn.com/content/v1/62965b4ce1b421641cf46e50/c27c7ff3-2980-4157-8440-c165eb31f768/group+lab+image.jpg https://www.burkhardtlab.org/projects daily 0.75 2022-10-26 https://images.squarespace-cdn.com/content/v1/62965b4ce1b421641cf46e50/36000dfd-641b-4642-b3b8-35993c5e394e/Cell+Forces.jpg Projects - Mechanobiology of the Immunological Synapse Research from our lab has revealed the existence of a tug-of-war that takes place at the immunological synapse, the cell-cell interface between T cells and dendritic cells. We found that centripetal actin flow on the T cell side of the synapse exerts force on the integrin LFA-1, inducing conformational changes that promote adhesion and promote T cell activation. Though the dendritic cell actin network is less dynamic, it restrains ligand mobility and stiffens the signaling platform, both of which augment T cell activation by resisting the forces exerted by the T cell. Ongoing work on this project is aimed at understanding how the cytoskeletal networks of the two cells contribute to receptor activation and signal integration. Representative Papers: Comrie WA, Babich A, Burkhardt JK. F-actin flow drives affinity maturation and spatial organization of LFA-1 at the immunological synapse. J Cell Biol. 2015 208:475-91. PMCID: PMC4332248. Comrie WA, Li S, Boyle S, Burkhardt JK. The dendritic cell cytoskeleton promotes T cell adhesion and activation by constraining ICAM-1 mobility. J Cell Biol. 2015 208:457-73. PMCID: PMC4332244. Jankowska KI, Williamson EK, Roy NH, Blumenthal D, Chandra V, Baumgart T, Burkhardt JK. Integrins Modulate T Cell Receptor Signaling by Constraining Actin Flow at the Immunological Synapse. Front. Immunol. 2018. DOI: 10.3389/fimmu.2018.00025 PMCID: PMC29403502 Blumenthal D, Chandra V, Burkhardt JK. T-cell priming is enhanced by maturation-dependent stiffening of the dendritic cell cortex. eLife 2020;9:e55995. 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