RoL: EAGER: DESYN-C3 Moving information across synthetic membranes via engineered sensors

Establishing pseudocells as a general platform will require technologies that decouple the flow of information from the flow of materials, while enabling bioengineers to link these phenomena to compose sophisticated sense and respond functions. Some applications may require using pseudocell membranes to isolate chemical species and catalysts within a pseudocell from the external environment. Inducing changes within the pseudocell, such as the initiation of a metabolic reaction cascade, could employ physical transport (e.g., diffusion or import of an inducer molecule), or physical processes (e.g., transmission of light), each of which is possible for a limited range of chemistries and applications. A far more powerful approach would be to mimic how living cells transduce information across membranes via transmembrane sensor proteins—coupling the presence of an environmental cue (e.g., detection of an analyte) to a change in cell state (e.g., initiation of a chemical reaction or induction of a genetic program), without moving materials across the membrane. However, it is not yet known how this universal biological mechanism may be recapitulated and harnessed for pseudocell engineering. This project will enable the construction of pseudocells that sense and respond to a diverse range of environmental cues without changing membrane permeability. Towards that end, a key objective of this project is to develop generalizable strategies for embedding engineered transmembrane sensors in synthetic membranes.