title: Do mechanical forces contribute to nanoscale membrane organisation in T cells?
abstract: Mechanotransduction describes how a cell senses and interacts with its environment. The concept originated in adhesion biology where adhesion receptors, integrins, facilitate force transmission between the extracellular matrix and the intracellular actin cytoskeleton. Indeed, during any adhesive contacts, cells do exert mechanical force. Hence, the probing of the local environment by cells results in mechanical cues that contribute to cellular functions and cell fate decisions such as migration, proliferation, differentiation and apoptosis. On the molecular level, mechanical forces can rearrange proteins laterally within the membrane, regulate their activity by inducing conformational changes and probe the mechanical properties and bond strength of receptor-ligands. From this point of view, it appears surprising that molecular forces have been largely overlooked in membrane organisation and ligand discrimination processes in lymphocytes. During T cell activation, the T cell receptor recognises and distinguishes antigenic from benign endogenous peptides to initiate the reorganisation of membrane proteins into signalling clusters within the immunological synapse. In this review, we asked whether characteristics of fibroblast force sensing could be applied to immune cell antigen recognition and signalling, and outline state-of-the-art experimental strategies for studying forces in the context of membrane organisation. This article is part of a Special Issue entitled: Nanoscale membrane orgainisation and signalling.
authors.affiliation: Centre for Vascular Research, ARC Centre of Excellence in Advanced Molecular Imaging and Australian Centre for Nanomedicine, University of New South Wales, Sydney, Australia. Electronic address: e.klotzsch@unsw.edu.au.
authors.forename: Enrico
authors.initials: E
authors.lastname: Klotzsch
authors.affiliation: Centre for Vascular Research, ARC Centre of Excellence in Advanced Molecular Imaging and Australian Centre for Nanomedicine, University of New South Wales, Sydney, Australia.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stiegler
authors.affiliation: Centre for Vascular Research, ARC Centre of Excellence in Advanced Molecular Imaging and Australian Centre for Nanomedicine, University of New South Wales, Sydney, Australia.
authors.forename: Eldad
authors.initials: E
authors.lastname: Ben-Ishay
authors.affiliation: Centre for Vascular Research, ARC Centre of Excellence in Advanced Molecular Imaging and Australian Centre for Nanomedicine, University of New South Wales, Sydney, Australia. Electronic address: k.gaus@unsw.edu.au.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gaus
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D018448:Models, Immunological; D053758:Nanoparticles / Q000737:chemistry*; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism*
keywords: Mechanobiology; Protein clustering; Signalling; Super-resolution fluorescence microscopy; T cell receptor; Traction force microscopy