Hormone-Responsive Electrodes for Quantitative Discourse with Endocrine Cells

Auburn University, Auburn AL

Investigators

Abstract

Proposal Number: 1403495 Principal Investigator: Christopher J. Easley Title: Hormone-Responsive Electrodes for Quantitative Discourse with Endocrine Cells General Biological systems communicate using cascades of molecular signals, exploiting numerous feedback control loops similar to automobile cruise control. To aid our understanding of these systems, there remains a need for materials that respond to biological signaling molecules such as proteins and DNA. We have developed measurement techniques (proximity assays) that can respond to very low levels of proteins, translate this signal into controlled DNA binding, then communicate the signal to an electrode for recording protein quantity. These techniques can also release DNA strands in proportional amounts to input proteins. The main objective of this proposal is to show that our surface-based proximity assays can sense hormone levels secreted by endocrine cells, then respond proportionally by releasing agents that modify secretion. Upon completion, we will have developed a tunable "cruise control" system for hormone secretion, one that should allow cell culture systems in the laboratory to more closely mimic their natural biological environment. Technical Our recently developed proximity-based protein assays are based on cooperative assembly of dual proximity probes, and they are highly sensitive and generalizable to essentially any protein with two available antibodies (or aptamers). These assays decouple target binding from the reporting mechanism by exploiting DNA hybridization and/or strand displacement reactions. We propose that our proximity assay format is amenable to two-way communication, rather than the one-way information transfer in typical biosensing systems. The objective of this proposal is to show that surface-based proximity assays can sense hormone levels secreted by endocrine cells, then respond proportionally by releasing agents that modify secretion. Such hormone-responsive electrodes could generate new paradigms in cell culture and allow endocrine tissue to be monitored in more in vivo like, responsive environments. Completion of our objective through the following goals will deliver transformative impacts in biosensing, responsive materials, and synthetic biology: 1) Develop an entirely surface-bound electrochemical proximity assay, 2) Synthesize functional DNA-drug conjugates, and 3) Develop hormone-responsive electrodes for quantitative communication from surfaces, through DNA circuits, and to living endocrine cells.