The past two decades have witnessed significant advances in the analysis of complex biological environments. Fluorescence imaging utilizing indicator dyes or proteins has played an important role but also suffers from significant limitations including toxicity, chemical stability and perturbation of the system. Though quite useful for a variety of ions and small molecules where fluorescent indicators or ionophores are available, large categories of chemically and biologically relevant analytes elude detection due to a lack of suitable indicators or lack of intrinsic optical or electrochemical activity. The use of membrane receptors, ion channels and molecular transporters in chemical sensing applications presents several potential advantages over traditional reporters as many such membrane proteins are highly selective to small molecule and/or protein based ligands and typically demonstrate high affinity binding that may translate to high sensitivity of the sensor. Here we propose a new class of nanometer-sized, biomimetic chemical sensors with embedded membrane proteins for intracellular, in vivo and environmental labeling, tracing and sensing applications. To realize such a sensor platform, we will create phospholipid vesicles from a series of lipids that can be chemically crosslinked and we will functionalize the vesicles with reconstituted membrane proteins. The key features of our sensor platform are: a) a phospholipid membrane formed from self assembly of polymerizable lipids and lipid composites; b) incorporated biological signal transduction elements, e.g. receptors; c) external membrane elements that serve to initiate cellular uptake and localization of the sensor; and d) indicator or reporter elements that serve to generate an optical signal. This modular sensor geometry will provide a general platform that can be utilized to readily design a wide variety of sensors.
