Tools for Monitoring and Modulating Cellular Communication

Abstract

Biological materials possess the ability to sense and change in response to diverse stimuli. This creates a spatially and temporally dynamic environment, presenting a barrier to investigation and intervention. As such, interfacing with living systems demands precision and adaptability. Here, we present novel technologies for monitoring and modulating the biochemical environment of multicellular tissues.

Neural and neuromuscular tissue offers both temporal and anatomical heterogeneity. Neuropathologies can arise from aberrant signaling from a single node; therefore targeting these structures directly for investigation and treatment is an attractive alternative to the standard systemic techniques. However, tissue response and device failure remain major challenges to local interfacing. Recent advances to our understanding of immune response to implantable materials has allowed for the development of technologies which promote minimal glial scarring while maintaining chronic function. To this end, we have developed modular neural implants for focal dosing, allowing for fine discrimination and investigation of proximal anatomical locations, such as the dorsal and ventral shell of the nucleus accumbens. These implants can be interfaced with our nanofluidic sampling platform for membraneless infusion and withdrawal of extracellular constituents at low flow rates. This allows for ‘liquid biopsies’ of the extracellular milieu and yields information on cellular signaling in healthy and diseased states in both in vitro and in vivo models.

Better monitoring of the cellular environment elucidates the relationship between proteomic signaling and function, informing the engineering of tissue-based sensors and therapies. We explored the use of implantable light-activated muscle for monitoring the response to exercise in both in vitro and in vivo models. These materials are able to integrate with native tissue and maintain their ability to respond to external, user-defined stimuli, thus creating multifunctional implants for monitoring and modulating cellular communication.