Cells are not only sensitive to dynamic mechanical stimuli such as strain or fluidic shear stress but are also sensitive to the mechanical properties of the substrate such as the stiffness. The range of ECM stiffness in the body is massive. Many orders of magnitude separate the softest tissue -the brain, with an elastic modulus of tenths of kPa-to the hardest -calcified bones with a modulus of the hundreds of MPa -and each specific cell type is tuned to the mechanical environment in which it resides. In particular, the stiffness of the cell microenvironment has a crucial role in many physiological and pathological processes of blood vessels as well as in the differentiation fate of stem cells . Bosworth et al. demonstrated that substrate stiffness influences the barrier function of the Blood-Brain barrier model. More specifically, iPSC-derived brain microvascular endotheliallike cells exhibit differences in passive but not in active barrier function in response to substrate stiffness. Recently, Zhou et al. observed significant vascular cell differences while remaining in a physiological range of substrate stiffness (18 vs 86 kPa). Compared with the 18 kPa substrate, on the 86 kPa substrate, the size of VECs increased, the production of NO decreased, the proliferation rate increased, and cells showed 560 differentially expressed genes, indicating that even a small increase in stiffness within the physiological range have a higher impact on vascular cell behaviors. Engler et al. looked at the relationship between substrate stiffness and mesenchymal stem cells (MSCs) differentiation, showing a dependency of the lineage of differentiation on the stiffness of the substrate. Indeed, soft PAA substrates with a stiffness of 0.1-1 kPa corresponding to brain tissue and 8-17 kPa corresponding to muscles led to neurogenic and myogenic differentiation respectively, while stiff substrates of 25-40 kPa induced osteogenic differentiation.