PDAC is characterized by complex physicochemical properties of the tumor microenvironment. Two of the key features are the altered mechanical properties of the fibrotic tumor stroma with its increased elasticity and tissue pressure as well as the unique pH landscape within the tumor and the surrounding normal pancreatic tissue. Activated pancreatic stellate cells largely contribute to the altered PDAC mechanics by secreting massive amounts of extracellular matrix proteins. Using a combination of live-cell (ionic) imaging, atomic force micropscopy and biochemical assays we aim to decipher mechanisms by which the pancreatic pH landscape regulates the ability of stellate cells to sense and respond to altered mechanical properties of the PDAC stroma.