Review: Bioengineering strategies to probe T cell mechanobiology

T cells play a major role in adaptive immune response, and T cell dysfunction can lead to the progression of several diseases that are often associated with changes in the mechanical properties of tissues. However, the concept that mechanical forces play a vital role in T cell activation and signaling is relatively new. The endogenous T cell microenvironment is highly complex and dynamic, involving multiple, simultaneous cell-cell and cell-matrix interactions. This native complexity has made it a challenge to isolate the effects of mechanical stimuli on T cell activation. In response, researchers have begun developing engineered platforms that recapitulate key aspects of the native microenvironment to dissect these complex interactions in order to gain a better understanding of T cell mechanotransduction. In this review, we first describe some of the unique characteristics of T cells and the mounting research that has shown they are mechanosensitive. We then detail the specific bioengineering strategies that have been used to date to measure and perturb the mechanical forces at play during T cell activation. In addition, we look at engineering strategies that have been used successfully in mechanotransduction studies for other cell types and describe adaptations that may make them suitable for use with T cells. These engineering strategies can be classified as 2D, so-called 2.5D, or 3D culture systems. In the future, findings from this emerging field will lead to an optimization of culture environments for T cell expansion and the development of new T cell immunotherapies for cancer and other immune diseases.