Mechanotransduction in T Cell Development, Differentiation and Function

• 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
• Journal Title: Cells
• Volume: Volume 9, Number 2
• Publisher: MDPI | 2020-02-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/cells9020364
• Subjects: Biology, Cell; Engineering, Biomedical; Engineering, Mechanical; Biology, Microbiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cell Biology; T cell antigen receptor; lymphocytes; thymocytes; catch bond; force; stiffness; Negative selection; Positive selection; Mechanical forces; Peptide MHC; Catch bonds; Thymocyte development; Signal transduction; Structural basis; TCR-Binding; Pre-TCR

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.