Nanomedical Relevance of the Intermolecular Interaction Dynamics—Examples from Lysozymes and Insulins

Ruiyan Zhang, Ning Zhang, Marzieh Mohri, Lisha Wu, Thomas Eckert, Vadim B. Krylov, Andrea Antosova, Slavomira Ponikova, Zuzana Bednarikova, Philipp Markart, Andreas Günther, Bengt Norden, Martin Billeter, Roland Schauer, Axel J. Scheidig, Bhisma N. Ratha, Anirban Bhunia, Karsten Hesse, Mushira Abdelaziz Enani, Jürgen SteinmeyerAthanasios K. Petridis, Tibor Kozar, Zuzana Gazova, Nikolay E. Nifantiev, Hans-Christian Siebert

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Insulin and lysozyme share the common features of being prone to aggregate and having biomedical importance. Encapsulating lysozyme and insulin in micellar nanoparticles probably would prevent aggregation and facilitate oral drug delivery. Despite the vivid structural knowledge of lysozyme and insulin, the environment-dependent oligomerization (dimer, trimer, and multimer) and associated structural dynamics remain elusive. The knowledge of the intra- and intermolecular interaction profiles has cardinal importance for the design of encapsulation protocols. We have employed various biophysical methods such as NMR spectroscopy, X-ray crystallography, Thioflavin T fluorescence, and atomic force microscopy in conjugation with molecular modeling to improve the understanding of interaction dynamics during homo-oligomerization of lysozyme (human and hen egg) and insulin (porcine, human, and glargine). The results obtained depict the atomistic intra- and intermolecular interaction details of the homo-oligomerization and confirm the propensity to form fibrils. Taken together, the data accumulated and knowledge gained will further facilitate nanoparticle design and production with insulin or lysozyme-related protein encapsulation.
Original languageEnglish (US)
Pages (from-to)4206-4220
Number of pages15
JournalACS Omega
Volume4
Issue number2
DOIs
StatePublished - Feb 27 2019
Externally publishedYes

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