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      Receptor-mediated cell mechanosensing

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          Abstract

          Mechanosensing depicts the ability of a cell to sense mechanical cues, which under some circumstances is mediated by the surface receptors. In this review, a four-step model is described for receptor-mediated mechanosensing. Platelet GPIb, T-cell receptor, and integrins are used as examples to illustrate the key concepts and players in this process.

          Abstract

          Mechanosensing describes the ability of a cell to sense mechanical cues of its microenvironment, including not only all components of force, stress, and strain but also substrate rigidity, topology, and adhesiveness. This ability is crucial for the cell to respond to the surrounding mechanical cues and adapt to the changing environment. Examples of responses and adaptation include (de)activation, proliferation/apoptosis, and (de)differentiation. Receptor-mediated cell mechanosensing is a multistep process that is initiated by binding of cell surface receptors to their ligands on the extracellular matrix or the surface of adjacent cells. Mechanical cues are presented by the ligand and received by the receptor at the binding interface; but their transmission over space and time and their conversion into biochemical signals may involve other domains and additional molecules. In this review, a four-step model is described for the receptor-mediated cell mechanosensing process. Platelet glycoprotein Ib, T-cell receptor, and integrins are used as examples to illustrate the key concepts and players in this process.

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          Most cited references204

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          Local force and geometry sensing regulate cell functions.

          The shapes of eukaryotic cells and ultimately the organisms that they form are defined by cycles of mechanosensing, mechanotransduction and mechanoresponse. Local sensing of force or geometry is transduced into biochemical signals that result in cell responses even for complex mechanical parameters such as substrate rigidity and cell-level form. These responses regulate cell growth, differentiation, shape changes and cell death. Recent tissue scaffolds that have been engineered at the micro- and nanoscale level now enable better dissection of the mechanosensing, transduction and response mechanisms.
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            T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases.

            Primary T-cell responses in lymph nodes (LNs) require contact-dependent information exchange between T cells and dendritic cells (DCs). Because lymphocytes continually enter and leave normal LNs, the resident lymphocyte pool is composed of non-synchronized cells with different dwell times that display heterogeneous behaviour in mouse LNs in vitro. Here we employ two-photon microscopy in vivo to study antigen-presenting DCs and naive T cells whose dwell time in LNs was synchronized. During the first 8 h after entering from the blood, T cells underwent multiple short encounters with DCs, progressively decreased their motility, and upregulated activation markers. During the subsequent 12 h T cells formed long-lasting stable conjugates with DCs and began to secrete interleukin-2 and interferon-gamma. On the second day, coinciding with the onset of proliferation, T cells resumed their rapid migration and short DC contacts. Thus, T-cell priming by DCs occurs in three successive stages: transient serial encounters during the first activation phase are followed by a second phase of stable contacts culminating in cytokine production, which makes a transition into a third phase of high motility and rapid proliferation.
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              The Principles of Engineering Immune Cells to Treat Cancer

              Chimeric antigen receptor (CAR) T cells have proven that engineered immune cells can serve as a powerful new class of cancer therapeutics. Clinical experience has helped to define the major challenges that must be met to make engineered T cells a reliable, safe, and effective platform that can be deployed against a broad range of tumors. The emergence of synthetic biology approaches for cellular engineering is providing us with a broadly expanded set of tools for programming immune cells. We discuss how these tools could be used to design the next generation of smart T cell precision therapeutics.
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                Author and article information

                Contributors
                Role: Monitoring Editor
                Journal
                Mol Biol Cell
                Mol. Biol. Cell
                molbiolcell
                mbc
                Mol. Bio. Cell
                Molecular Biology of the Cell
                The American Society for Cell Biology
                1059-1524
                1939-4586
                07 November 2017
                : 28
                : 23
                : 3134-3155
                Affiliations
                [1] aWoodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332
                [2] bParker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332
                [3] dCoulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332
                [4] cCharles Perkins Centre and Heart Research Institute, University of Sydney, Camperdown, NSW 2006, Australia
                University of California, San Francisco
                Author notes

                The authors have no conflicting interests to declare.

                These authors should be regarded as joint first authors.

                Present address: Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037.

                *Address correspondence to: Cheng Zhu ( cheng.zhu@ 123456bme.gatech.edu ).
                Article
                E17-04-0228
                10.1091/mbc.E17-04-0228
                5687017
                28954860
                c7bf8917-adda-4347-8cbc-4a09ff8b3a39
                © 2017 Chen, Ju, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License ( http://creativecommons.org/licenses/by-nc-sa/3.0).

                “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.

                History
                : 10 April 2017
                : 06 September 2017
                : 19 September 2017
                Categories
                Special Article

                Molecular biology
                Molecular biology

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