Monitoring Disassembly and Cargo Release of Phase-Separated Peptide Coacervates with Native Mass Spectrometry

Carmine P. Cerrato, Axel Leppert, Yue Sun, David P. Lane, Marie Arsenian-Henriksson, Ali Miserez*, Michael Landreh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Engineering liquid-liquid phase separation (LLPS) of proteins and peptides holds great promise for the development of therapeutic carriers with intracellular delivery capability but requires accurate determination of their assembly properties in vitro, usually with fluorescently labeled cargo. Here, we use mass spectrometry (MS) to investigate redox-sensitive coacervate microdroplets (the dense phase formed during LLPS) assembled from a short His- and Tyr-rich peptide. We can monitor the enrichment of a reduced peptide in dilute phase as the microdroplets dissolve triggered by their redox-sensitive side chain, thus providing a quantitative readout for disassembly. Furthermore, MS can detect the release of a short peptide from coacervates under reducing conditions. In summary, with MS, we can monitor the disassembly and cargo release of engineered coacervates used as therapeutic carriers without the need for additional labels.

Original languageEnglish
Pages (from-to)10869-10872
Number of pages4
JournalAnalytical Chemistry
Volume95
Issue number29
DOIs
Publication statusPublished - Jul 25 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.

ASJC Scopus Subject Areas

  • Analytical Chemistry

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