Stimulus-responsive elastin-like polypeptides (ELPs) grafted onto surfaces are of significant technical interest because they can be exploited for force generation, in sensing applications, or as molecular switches with tunable properties. Changes in the conformational state of grafted ELPs, induced by a phase transition or changes in osmotic pressure, lead to significant changes in the surface stress in the ELP graft layer and translate into detectable changes in microcantilever deflection. In this study, we investigate the conformational mechanics of ELPs in response to changes in solution pH and ionic strength using atomic force microscopy (AFM) microcantilever deflection and quartz crystal microbalance (QCM) measurements. We show that the use of genetically encoded, surface-grafted ELPs is exciting for cantilever actuation and sensing because commonly available microfabricated cantilever springs offer a simple and nonintrusive way to detect changes in solvent type, temperature, and pH, promising great potential for sensing applications in microfluidic devices.