Mechanical forces play a critical role in modulating many cellular processes. 1 Once cells experience mechanical stimuli, including substrate rigidity, external forces, and endogenous forces, they dynamically transduce the mechanical input into biochemical signals. With these signals, cells adapt and respond to their microenvironments, as well as make decisions involving activation, migration, proliferation, differentiation, and apoptosis (Figure 3.1 A). 2 These processes, known as mechanosensing and mechanotransduction, have been observed in various cells, including platelets, cancer cells, stem cells, and immune cells. 3 Receptors on the cell surface, including integrins, notch, T cell receptor (TCR), and B cell receptor (BCR), participate intensively in mechanically sensing the environment and guide the cell through decision-making processes. 4–7 This chapter will start with an introduction of cell receptor force transduction, specifically force interplay between integrins and T cell receptor and their ligands, as well as its role in the cellular response. Then we will introduce tools that have been