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

Zhang R, Zhang N, Mohri M, Wu L, Eckert T, Krylov VB, Antosova A, Ponikova S, Bednarikova Z, Markart P, G√ľnther A, Norden B, Billeter M, Schauer R, Scheidig AJ, Ratha BN, Bhunia A, Hesse K, Enani MA, Steinmeyer J, Petridis AK, Kozar T, Gazova Z, Nifantiev NE, Siebert HC

ACS Omega 4 (2) 4206-4220 [2019-02-28; online 2019-02-27]

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.

Swedish NMR Centre (SNC) [Service]

PubMed 30847433

DOI 10.1021/acsomega.8b02471

Crossref 10.1021/acsomega.8b02471

pmc: PMC6398350

Publications 9.5.0