Dendrimer Conjugation Enables Multiphoton Chemical Neurophysiology Studies with an Extended ?-Electron Caging Chromophore.

ABSTRACT: We have developed a caged neurotransmitter using an extended ?-electron chromophore for efficient multiphoton uncaging on living neurons. Widely studied in a chemical context, such chromophores are inherently bioincompatible due to their highly lipophilic character. Attachment of two polycarboxylate dendrimers, a method we call "cloaking", to a bisstyrylthiophene (or BIST) core effectively transformed the chromophore into a water-soluble optical probe, whilst maintaining the high two-photon absorption of over 500?GM. Importantly, the cloaked caged compound was biologically inert at the high concentrations required for multiphoton chemical physiology. Thus, in contrast to non-cloaked BIST compounds, the BIST-caged neurotransmitter can be safely delivered onto neurons in acutely isolated brain slices, thereby enabling high-resolution two-photon uncaging without any side effects. We expect that our cloaking method will enable the development of new classes of cell-compatible photolabile probes using a wide variety of extended ?-electron caging chromophores.

SUBMITTER: Richers MT 

PROVIDER: S-EPMC6707848 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature