Mechanotransduction in T Cell Development, Differentiation and Function

• Type of Material: Article
• Authors: Muaz Rushdi, Georgia Institute of Technology; Kaitao Li, Georgia Institute of Technology; Zhou Yuan, Georgia Institute of Technology; Stefano Travaglino, Georgia Institute of Technology; Arash Grakoui, Emory University; Cheng Zhu, Emory University
• Language: English
• Date: 2020-02-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/cells9020364
• Title of Journal or Parent Work: Cells
• Volume: 9
• Issue: 2
• Grant/Funding Information: This project was funded by the US National Institutes of Health (NIH) grant number R01GM122489, R21Al135753, R01AI124680, and U01CA214354.
• Keywords: Signal transduction; Life Sciences & Biomedicine; Cell Biology; Science & Technology; Catch bonds; Structural basis; Thymocyte development; catch bond; lymphocytes; Pre-TCR; Positive selection; Peptide MHC; thymocytes; stiffness; Negative selection; Mechanical forces; TCR-Binding; force; T cell antigen receptor
• Research Categories: Engineering, Biomedical; Biology, Microbiology; Biology, Cell; Engineering, Mechanical

Abstract

Cells in the body are actively engaging with their environments that include both biochemical and biophysical aspects. The process by which cells convert mechanical stimuli from their environment to intracellular biochemical signals is known as mechanotransduction. Exemplifying the reliance on mechanotransduction for their development, differentiation and function are T cells, which are central to adaptive immune responses. T cell mechanoimmunology is an emerging field that studies how T cells sense, respond and adapt to the mechanical cues that they encounter throughout their life cycle. Here we review different stages of the T cell's life cycle where existing studies have shown important effects of mechanical force or matrix stiffness on a T cell as sensed through its surface molecules, including modulating receptor-ligand interactions, inducing protein conformational changes, triggering signal transduction, amplifying antigen discrimination and ensuring directed targeted cell killing. We suggest that including mechanical considerations in the immunological studies of T cells would inform a more holistic understanding of their development, differentiation and function.