Bidirectional biomimetic interfaces for the in vitro exploration of human physiology

BBSRC strategic theme: Transformative technologies

Communication, defined as the exchange of information between entities, plays an essential role not only at the societal but also cellular level, facilitating the progression of complexity and intelligence. As physiological functions and mechanisms become increasingly sophisticated, scientists encounter greater challenges in comprehensively investigating and understanding them. In vitro models offer a means to alleviate this complexity by faithfully replicating relevant in vivo characteristics while striking a balance between simplicity and accuracy, thereby enhancing biological relevance and statistical robustness of experimental outcomes. However, the utility of these models is constrained by the tools available for communicating with these models, i.e. investigation and interaction techniques. Given the distinct languages spoken by humans and cells, a bidirectional interface, akin to a language translator, is essential to enable the exchange of information between cells and humans.
Bioelectronics has emerged as a promising avenue for constructing such bidirectional interfaces, enabling continuous, label-free monitoring and precise control of biological activity. By translating chemical and electrical signals, both pivotal players in cellular communication, bioelectronics facilitates a deeper understanding of and better control over cellular processes. Unlike conventional in vitro systems, which are often assessed through infrequent measurements and manual interventions, system integration of bidirectional interfaces opens new avenues for developing sophisticated tools that provide deeper insights into biological systems. Moreover, combining bioelectronics with biomimetic approaches leverages nature's solutions such as membrane receptors for signal transduction utilised in bioelectronic sensing with biomembranes or electrical cell stimulation, thereby bridging the formidable capabilities of biology and electronics.

The primary objective of this project is the system integration of bidirectional biomimetic interfaces in regulatory pathway models to explore human physiology in vitro. While developing a platform that can be tailored to various physiological pathways by leveraging the advantages of biomimetic bioelectronic approaches for interfacing with biological structures presents the ultimate goal, demonstration of its capabilities will be achieved by initially focusing on one specific systemic pathway of human physiology. The gut-brain axis presents an intriguing candidate for such a system, given its widespread connections throughout the body and indications of influence on information processing, which recently received a great deal of attention. With electrical and chemical signals exchanged across bodily distances, this system offers a fittingly complex model. Specifically, the serotonin pathway, characterised by its profound systemic effects, poses challenges for isolated investigation in animal models. Developing a platform that mimics relevant features of this pathway would provide valuable insights in the complex interplay between gut and brain.

Thus, relevant cell lines involved in the serotonin pathway should be co-cultured within a microphysiological system to model a facet of the gut-brain axis in vitro. Concurrently, a bidirectional biomimetic interface, incorporating bioelectronic elements such as biomembrane sensors and electrical cell stimulation, should be seamlessly integrated to enable continuous monitoring and precise modulation of systemic behaviour. A platform as the one proposed here holds promise for advancing our understanding of and communication capabilities with living systems, which facilitates subsequent interventions and leverages technology to enhance knowledge and human well-being.