Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 22, Pages 12258-12263Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202016105
Keywords
directionality; early endosomes; fluorescent probes; mechanosensitivity; membrane penetration; pH gradients
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Funding
- University of Geneva
- Swiss National Centre of Competence in Research (NCCR) Molecular Systems Engineering
- NCCR Chemical Biology
- Swiss NSF
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Researchers have developed a rational strategy to target early endosomes using a substituted benzylamine with a higher pKa value as the head group of flipper probes. This allows for preserved mechanosensitivity and can be used to elucidate the mechanics of endocytosis in biology.
Fluorescent flipper probes have been introduced recently to image membrane tension in live cells, and strategies to target these probes to specific membranes are emerging. In this context, early endosome (EE) targeting without the use of protein engineering is especially appealing because it translates into a fascinating transport problem. Weakly basic probes, commonly used to track the inside of acidic late endosomes and lysosomes, are poorly retained in EE because they are sufficiently neutralized in weakly acidic EE, thus able to diffuse out. Here, we disclose a rational strategy to target EE using a substituted benzylamine with a higher pK(a) value as a head group of the flipper probe. The resulting EE flippers are validated for preserved mechanosensitivity, ready for use in biology, particularly to elucidate the mechanics of endocytosis.
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