NeuM: A Neuron-Selective Probe Incorporates into Live Neuronal Membranes via Enhanced Clathrin-Mediated Endocytosis in Primary Neurons

Yoonsik Sung, Lizaveta Gotina, Kyu Hyeon Kim, Jung Yeol Lee, Seulgi Shin, Hira Aziz, Dong Min Kang, Xiao Liu, Na Kyeong Hong, Hong Guen Lee, Jun Seok Lee, Hyeyeong Ku, Cherlhyun Jeong, Ae Nim Pae, Sungsu Lim, Young Tae Chang, Yun Kyung Kim

Research output: Contribution to journalArticlepeer-review

Abstract

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined. Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons. In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001). Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin-mediated endocytosis. Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61). Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers. The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures.

Original languageEnglish
Article numbere202312942
JournalAngewandte Chemie - International Edition
Volume63
Issue number3
DOIs
Publication statusPublished - 2024 Jan 15

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Keywords

  • Clathrin-Mediated Endocytosis
  • Endocytic Trafficking
  • Fluorescent Probe
  • Membrane
  • Neuron

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry

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