A key goal of bottom-up synthetic biology is to construct cell- and tissue-like structures. Underpinning cellular life is the ability to process several external chemical signals, often in parallel. Until now, cell- and tissue-like structures have been constructed with no more than one signaling pathway. Many pathways rely on signal transport across membranes using protein nanopores. However, such systems currently suffer from the slow transport of molecules. We have optimized the application of these nanopores to permit fast molecular transport, which has allowed us to construct a processor for parallel chemical signals from the bottom up in a modular fashion. The processor comprises three aqueous droplet compartments connected by lipid bilayers and operates in an aqueous environment. It can receive two chemical signals from the external environment, process them orthogonally, and then produce a distinct output for each signal. It is suitable for both sensing and enzymatic processing of environmental signals, with fluorescence and molecular outputs. In the future, such processors could serve as smart drug delivery vehicles or as modules within synthetic tissues to control their behavior in response to external chemical signals.
Keywords: alpha hemolysin; droplet interface bilayers (DIBs); drug delivery; multisomes; nanopores; sensors; synthetic biology.