title: Enzyme-linked DNA dendrimer nanosensors for acetylcholine.
abstract: It is currently difficult to measure small dynamics of molecules in the brain with high spatial and temporal resolution while connecting them to the bigger picture of brain function. A step towards understanding the underlying neural networks of the brain is the ability to sense discrete changes of acetylcholine within a synapse. Here we show an efficient method for generating acetylcholine-detecting nanosensors based on DNA dendrimer scaffolds that incorporate butyrylcholinesterase and fluorescein in a nanoscale arrangement. These nanosensors are selective for acetylcholine and reversibly respond to levels of acetylcholine in the neurophysiological range. This DNA dendrimer architecture has the potential to overcome current obstacles to sensing in the synaptic environment, including the nanoscale size constraints of the synapse and the ability to quantify the spatio-temporal fluctuations of neurotransmitter release. By combining the control of nanosensor architecture with the strategic placement of fluorescent reporters and enzymes, this novel nanosensor platform can facilitate the development of new selective imaging tools for neuroscience.
authors.affiliation: Dept of Pharmaceutical Sciences, Northeastern University, 206 The Fenway, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Walsh
authors.affiliation: Dept of Pharmaceutical Sciences, Northeastern University, 206 The Fenway, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Morales
authors.affiliation: Dept of Pharmaceutical Sciences, Northeastern University, 206 The Fenway, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Skipwith
authors.affiliation: Dept of Pharmaceutical Sciences, Northeastern University, 206 The Fenway, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Timothy T
authors.initials: TT
authors.lastname: Ruckh
authors.affiliation: Dept of Pharmaceutical Sciences, Northeastern University, 206 The Fenway, 360 Huntington Avenue, Boston, MA 02115, USA.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Clark
mesh_terms: D000109:Acetylcholine / Q000737:chemistry / Q000378:metabolism*; D015374:Biosensing Techniques / Q000379:methods*; D002091:Butyrylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D019793:Fluorescein / Q000737:chemistry / Q000378:metabolism; D005949:Glucose Oxidase / Q000737:chemistry / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D050091:Dendrimers; D004247:DNA; D005949:Glucose Oxidase; D002091:Butyrylcholinesterase; D000109:Acetylcholine; D019793:Fluorescein