Engineered Protein Copolymers for Heparin Neutralization and Detection

Qing Liu, Ahmed Shaukat, Zhuojung Meng, Sami Nummelin, Tekla Tammelin, Eero Kontturi, Renko de Vries, Mauri A. Kostiainen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Heparin is a widely applied anticoagulant agent.
However, in clinical practice, it is of vital importance to reverse its anticoagulant effect to restore the blood-clotting cascade and circumvent side effects. Inspired by protein cages that can encapsulate and protect their cargo from surroundings, we utilize three designed protein copolymers to sequester heparin into inert nanoparticles. In our design, a silk-like sequence provides cooperativity between proteins, generating a multivalency effect that enhances the heparin-binding ability. Protein copolymers complex heparin into well-defined nanoparticles with diameters below 200 nm. We also develop a competitive fluorescent switch-on assay for heparin detection, with a detection limit of 0.01 IU mL−1 in plasma that is significantly below the therapeutic range (0.2−8 IU mL−1). Moreover, moderate cytocompatibility is demonstrated by in vitro cell studies. Therefore, such engineered protein copolymers present a promising alternative for neutralizing and sensing heparin, but further optimization is required for in vivo applications.
Original languageEnglish
Number of pages8
JournalBiomacromolecules
DOIs
Publication statusE-pub ahead of print - 4 Jan 2023
MoE publication typeA1 Journal article-refereed

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