Microphysiological systems (MPSs) replicate essential biological processes and cellular responses in vitro, mirroring the in vivo behavior of cells, tissues, and organs. Within the body, cells experience biomechanical stimuli that vary depending on the type of tissue and may change in response to disease or injury. Biomechanical forces, such as shear stress, compression, and cyclic stretching, play a crucial role in regulating cell behavior, potentially enhancing, negating, or even reversing responses to biochemical signals or drug candidates. Replicating such stresses is essential for accurately modeling in vivo behavior in these systems. In MISS, we will focus on the effects of mechanical loading in MPSs resembling the synovium, the key actor in an important autoimmune disease, i.e. rheumatoid arthritis (RA). Starting from patient-derived cells, the role of mechanical stresses in the progression of the molecular processes in RA will be elucidated.