Biphasic mechanosensitivity of T cell receptor-mediated spreading of lymphocytes
| Autor: | Laurent Limozin, Pierre Dillard, Kheya Sengupta, Céline Dinet, Pierre-Henri Puech, Astrid Wahl, Aya Nassereddine |
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| Přispěvatelé: | Laboratoire de chimie bactérienne (LCB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Adhésion et Inflammation (LAI), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2019 |
| Předmět: |
T cell
T-Lymphocytes Integrin Receptors Antigen T-Cell 02 engineering and technology Myosins Ligands Mechanotransduction Cellular Cell Line Substrate Specificity 03 medical and health sciences Mechanobiology medicine Humans Cell adhesion Receptor ComputingMilieux_MISCELLANEOUS Actin 030304 developmental biology [PHYS]Physics [physics] 0303 health sciences Immunity Cellular Multidisciplinary biology Chemistry Ligand T-cell receptor 021001 nanoscience & nanotechnology Kinetics medicine.anatomical_structure Physical Sciences Biophysics biology.protein [SDV.IMM]Life Sciences [q-bio]/Immunology 0210 nano-technology |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2019, 116 (13), pp.5908-5913. ⟨10.1073/pnas.1811516116⟩ Proceedings of the National Academy of Sciences of the United States of America, 2019, 116 (13), pp.5908-5913. ⟨10.1073/pnas.1811516116⟩ |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1811516116⟩ |
| Popis: | Mechanosensing by T cells through the T cell receptor (TCR) is at the heart of immune recognition. While the mechanobiology of the TCR at the molecular level is increasingly well documented, its link to cell-scale response is poorly understood. Here we explore T cell spreading response as a function of substrate rigidity and show that remarkably, depending on the surface receptors stimulated, the cellular response may be either biphasic or monotonous. When adhering solely via the TCR complex, T cells respond to environmental stiffness in an unusual fashion, attaining maximal spreading on an optimal substrate stiffness comparable to that of professional antigen-presenting cells. However, in the presence of additional ligands for the integrin LFA-1, this biphasic response is abrogated and the cell spreading increases monotonously with stiffness up to a saturation value. This ligand-specific mechanosensing is effected through an actin-polymerization-dependent mechanism. We construct a mesoscale semianalytical model based on force-dependent bond rupture and show that cell-scale biphasic or monotonous behavior emerges from molecular parameters. As the substrate stiffness is increased, there is a competition between increasing effective stiffness of the bonds, which leads to increased cell spreading and increasing bond breakage, which leads to decreased spreading. We hypothesize that the link between actin and the receptors (TCR or LFA-1), rather than the ligand/receptor linkage, is the site of this mechanosensing. |
| Databáze: | OpenAIRE |
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