Towards a Biohybrid Device: Engineering Gap Junctions and Induced Neurons

Abstract

The new subfield of biohybrid device engineering for brain computer interface applicationshas emerged recently. With a large focus placed on microfabrication aspect, relatively little attention has been given so far to the most complex and least understood part of the device - its biological component. In my thesis work, I aim to better understand the basic science behind two biological components of the target device: electrical synapses and induced neurons. My aspiration is to advance our understanding of the underlying biology such that it can subsequently be reduced to engineering. To do so, I employ a variety of techniques, from molecular dynamics simulation to in vitro and in vivo characterization of engineered cells and proteins. I was able to identify a residue-wise docking interaction pattern for Cx34.7 and Cx35, and modify it to act in a heterotypic exclusive way. I was also able to establish a framework for cellular engineering that quantifies the homogeneity of the resulting neuronal population. When extended further, such framework can be used for streamlined and iterative cellular engineering to obtain a narrowly-defined neuronal subtype for the ultimate biohybrid device.