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

RY Zhang and N Zhang and M Mohri and LS Wu and T Eckert and VB Krylov and A Antosova and S Ponikova and Z Bednarikova and P Markart and A Gunther and B Norden and M Billeter and R Schauer and AJ Scheidig and BN Ratha and A Bhunia and K Hesse and MA Enani and J Steinmeyer and AK Petridis and T Kozar and Z Gazova and NE Nifantiev and HC Siebert, ACS OMEGA, 4, 4206-4220 (2019).

DOI: 10.1021/acsomega.8b02471

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.

Return to Publications page