CURIES has established a state-of-the-art experimental platform for advanced modelling of biomechanical events in the urothelium. The project was founded on the hypothesis that hypersensitive bladder disorders associated with urinary tract infections (UTIs) arise, at least in part, from impaired urothelial mechanotransduction—the ability of the urothelium to sense and decode mechanical tension. Existing microfluidic systems that model stretching cellular systems simulate expansive processes through a uniaxial pulling of a flexible substrate to which cellular models are adhered. While valuable, these approaches do not accurately reproduce the physiological forces experienced by the urothelium in vivo. CURIES overcomes this limitation through a pressure-driven microfluidic design that applies isotropic stretching from the apical direction, closely mimicking bladder filling dynamics. We propose that this mode of stimulation is essential for activating physiologically relevant mechanosensory pathways and signalling networks in urothelial cells.
With the validation of the model, showing it to be amenable to controlled stretching and to respond biomimetically, future work will be to use it for discovery, as there exist no tractable experimental system to study human urothelial biomechanics. Profiling the proteome and phosphoproteome, will be a powerful route to identify mechanosensors, signalling intermediates and downstream effectors. From these data benchmarks of critical reference framework of healthy urothelial biomechanics can be set, against which to decipher how they are then impacted by serious disease. While the current single-unit prototype is well suited to exploratory studies and the identification of potential therapeutic targets, widespread adoption across academic and industrial research environments will necessitate the development of a scalable, parallelised microfluidic platform capable of supporting higher-throughput experimentation. Furthermore, the platform provides a foundation for the development of in vitro pipelines to optimise bacteriophage-based therapies targeting antimicrobial-resistant pathogens. By integrating physiologically relevant host-tissue models with infection biology, the technology will be used to accelerate the identification and refinement of phage candidates and support the development of precision antimicrobial strategies.
