Nano-guided Cell Networks as Conveyors of Molecular Information

Molecular communications open new doors
connecting microelectronic devices and
biological systems

IBBR Bioengineering faculty and collaborators are exploiting synthetic biology to enable “cell-todevice” communication. Synthetic biology is often visualized as an innovative means for “green” product synthesis through the genetic rearrangement of cells, endowing them with novel biosynthetic capability. An alternative vision recognizes a cell’s ability to access biological information and tune biosynthetic capabilities and regulatory networks for facilitating information flow and coordinating cell-based output. That is, cells can be rewired to survey and report on their molecular “space” as they have sophisticated capabilities to recognize, amplify, and transduce chemical information. Further, they provide a means

to connect biological systems with traditional microelectronic devices and in doing so, present a potential interface between chemically-based biological information processing and conventional vectors of information flow, such as electrons and photons. Specifically, through clever designs, cell-based molecular information “processors” can be coupled to enable device-born abiotic responses. Cells then represent a versatile means for mediating the molecular “signatures” common in complex environments. In other words, they are conveyors of molecular communication.

In Terrell et al., Nature Communications (doi:10.1038/ncomms9500, October 12, 2015), researchers developed a network of cells that can be deployed in complex environments and report on the concentration of signal molecules. Specifically, cells are engineered to express different fluorescent proteins in response to different concentrations. At the same time, they express on their outer surfaces, a binding peptide that enables linkage to magnetic nanoparticles. In this way, surveyor cells can respond to their environment, be collected by a magnet, and “read” by optical or electronic means. Their work is the first of its kind to combine synthetic biology and nanoparticle processes for the interrogation of complex environmental niches. Through a multi-million dollar grant from the US Defense Threat Reduction Agency (DTRA), IBBR Bioengineering faculty William Bentley and Gregory Payne are collaborating with Matthew Chang (Singapore) and John March (Cornell) to develop “smart” bacteria that would interrogate the GI tract, seek pathogens, and then take steps to eradicate them. In order to develop this concept, they have worked for to unravel the complex signal transduction processes that mediate interbacterial communication – that is, the mechanisms by which bacteria ‘talk’ to their neighbors. In a process known as “quorum sensing (QS)”, bacterial intercellular communication is used to alter behavior so that individual cells operate more like a coordinated collection of cells. The mechanisms by which they evade antibiotic treatments are sometimes regulated by this communication system. QS is mediated by the secretion and perception of small molecules. In a sense, this represents “molecular communication” as opposed to what we most often use to process information flow: pressure waves (sound) between humans, electrons and photons (electronics) between devices.