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 Steinmeyer; Athanasios K. Petridis; Tibor Kozar; Zuzana Gazova; Nikolay E. Nifantiev; Hans-Christian Siebert

doi:10.1021/acsomega.8b02471

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 journal › Article › peer-review

14 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 language	English (US)
Pages (from-to)	4206-4220
Number of pages	15
Journal	ACS Omega
Volume	4
Issue number	2
DOIs	https://doi.org/10.1021/acsomega.8b02471
State	Published - Feb 27 2019
Externally published	Yes

Bibliographical note

KAUST Repository Item: Exported on 2021-03-12
Acknowledged KAUST grant number(s): KUK-11-008-23
Acknowledgements: This work was supported by the Open Project of Shandong Collaborative Innovation Center for Antibody Drugs (No. CIC-AD1834) and Tai-Shan Scholar Research Fund of Shandong Province of China. This work was also technically supported by Engineering Research Center for Nanomedicine and Drug Delivery Systems. The Swedish NMR Centre is acknowledged for supplying instrument time and support. This work was supported by the King Abdullah University of Science and Technology (grant KUK-11-008-23 awarded to B.N. with Ph.D. position for L.W.) and the European Research Council (ERC-2008-AdG 227700 to B.N.). We thank the Sialic Acids Society for financial support. Parts of the work were supported by RSF grant 14-23-00199 (NEN). On the Slovak side, the work was supported by project VEGA 2/0145/17, 2/0030/18, and SAS-MOST JRP 2015/5. This work was partly supported by Council of Scientific and Industrial Research (CSIR), Govt. of India (02(0292)/17/EMR-II) (to AB). Supports from EU projects 26220120033, 26210120002, 26110230097, and 26210120012 (IEP SAS Kosice, Slovakia) are gratefully acknowledged. We also thank Prof. Dr Frank D Sonnichsen (Otto Diels Institute for Organic Chemistry, Christian Albrechts University, Kiel, Germany) for his helpful support with respect to some of our NMR experiments. Last but not least, Dr Anna Kozarova (University of Windsor, Windsor, Ontario Canada) is highly acknowledged for critical reading and helpful comments on the manuscript.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

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10.1021/acsomega.8b02471

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Zhang, R., Zhang, N., Mohri, M., Wu, L., Eckert, T., Krylov, V. B., Antosova, A., Ponikova, S., Bednarikova, Z., Markart, P., Günther, A., Norden, B., Billeter, M., Schauer, R., Scheidig, A. J., Ratha, B. N., Bhunia, A., Hesse, K., Enani, M. A., ... Siebert, H.-C. (2019). Nanomedical Relevance of the Intermolecular Interaction Dynamics—Examples from Lysozymes and Insulins. ACS Omega, 4(2), 4206-4220. https://doi.org/10.1021/acsomega.8b02471

@article{d712eced21c945c798771a415267a7a9,

title = "Nanomedical Relevance of the Intermolecular Interaction Dynamics—Examples from Lysozymes and Insulins",

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.",

author = "Ruiyan Zhang and Ning Zhang and Marzieh Mohri and Lisha Wu and Thomas Eckert and Krylov, {Vadim B.} and Andrea Antosova and Slavomira Ponikova and Zuzana Bednarikova and Philipp Markart and Andreas G{\"u}nther and Bengt Norden and Martin Billeter and Roland Schauer and Scheidig, {Axel J.} and Ratha, {Bhisma N.} and Anirban Bhunia and Karsten Hesse and Enani, {Mushira Abdelaziz} and J{\"u}rgen Steinmeyer and Petridis, {Athanasios K.} and Tibor Kozar and Zuzana Gazova and Nifantiev, {Nikolay E.} and Hans-Christian Siebert",

note = "KAUST Repository Item: Exported on 2021-03-12 Acknowledged KAUST grant number(s): KUK-11-008-23 Acknowledgements: This work was supported by the Open Project of Shandong Collaborative Innovation Center for Antibody Drugs (No. CIC-AD1834) and Tai-Shan Scholar Research Fund of Shandong Province of China. This work was also technically supported by Engineering Research Center for Nanomedicine and Drug Delivery Systems. The Swedish NMR Centre is acknowledged for supplying instrument time and support. This work was supported by the King Abdullah University of Science and Technology (grant KUK-11-008-23 awarded to B.N. with Ph.D. position for L.W.) and the European Research Council (ERC-2008-AdG 227700 to B.N.). We thank the Sialic Acids Society for financial support. Parts of the work were supported by RSF grant 14-23-00199 (NEN). On the Slovak side, the work was supported by project VEGA 2/0145/17, 2/0030/18, and SAS-MOST JRP 2015/5. This work was partly supported by Council of Scientific and Industrial Research (CSIR), Govt. of India (02(0292)/17/EMR-II) (to AB). Supports from EU projects 26220120033, 26210120002, 26110230097, and 26210120012 (IEP SAS Kosice, Slovakia) are gratefully acknowledged. We also thank Prof. Dr Frank D Sonnichsen (Otto Diels Institute for Organic Chemistry, Christian Albrechts University, Kiel, Germany) for his helpful support with respect to some of our NMR experiments. Last but not least, Dr Anna Kozarova (University of Windsor, Windsor, Ontario Canada) is highly acknowledged for critical reading and helpful comments on the manuscript. This publication acknowledges KAUST support, but has no KAUST affiliated authors.",

year = "2019",

month = feb,

day = "27",

doi = "10.1021/acsomega.8b02471",

language = "English (US)",

volume = "4",

pages = "4206--4220",

journal = "ACS Omega",

issn = "2470-1343",

publisher = "American Chemical Society",

number = "2",

}

Zhang, R, Zhang, N, Mohri, M, Wu, L, Eckert, T, Krylov, VB, Antosova, A, Ponikova, S, Bednarikova, Z, Markart, P, Günther, 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, H-C 2019, 'Nanomedical Relevance of the Intermolecular Interaction Dynamics—Examples from Lysozymes and Insulins', ACS Omega, vol. 4, no. 2, pp. 4206-4220. https://doi.org/10.1021/acsomega.8b02471

TY - JOUR

T1 - Nanomedical Relevance of the Intermolecular Interaction Dynamics—Examples from Lysozymes and Insulins

AU - Zhang, Ruiyan

AU - Zhang, Ning

AU - Mohri, Marzieh

AU - Wu, Lisha

AU - Eckert, Thomas

AU - Krylov, Vadim B.

AU - Antosova, Andrea

AU - Ponikova, Slavomira

AU - Bednarikova, Zuzana

AU - Markart, Philipp

AU - Günther, Andreas

AU - Norden, Bengt

AU - Billeter, Martin

AU - Schauer, Roland

AU - Scheidig, Axel J.

AU - Ratha, Bhisma N.

AU - Bhunia, Anirban

AU - Hesse, Karsten

AU - Enani, Mushira Abdelaziz

AU - Steinmeyer, Jürgen

AU - Petridis, Athanasios K.

AU - Kozar, Tibor

AU - Gazova, Zuzana

AU - Nifantiev, Nikolay E.

AU - Siebert, Hans-Christian

N1 - KAUST Repository Item: Exported on 2021-03-12 Acknowledged KAUST grant number(s): KUK-11-008-23 Acknowledgements: This work was supported by the Open Project of Shandong Collaborative Innovation Center for Antibody Drugs (No. CIC-AD1834) and Tai-Shan Scholar Research Fund of Shandong Province of China. This work was also technically supported by Engineering Research Center for Nanomedicine and Drug Delivery Systems. The Swedish NMR Centre is acknowledged for supplying instrument time and support. This work was supported by the King Abdullah University of Science and Technology (grant KUK-11-008-23 awarded to B.N. with Ph.D. position for L.W.) and the European Research Council (ERC-2008-AdG 227700 to B.N.). We thank the Sialic Acids Society for financial support. Parts of the work were supported by RSF grant 14-23-00199 (NEN). On the Slovak side, the work was supported by project VEGA 2/0145/17, 2/0030/18, and SAS-MOST JRP 2015/5. This work was partly supported by Council of Scientific and Industrial Research (CSIR), Govt. of India (02(0292)/17/EMR-II) (to AB). Supports from EU projects 26220120033, 26210120002, 26110230097, and 26210120012 (IEP SAS Kosice, Slovakia) are gratefully acknowledged. We also thank Prof. Dr Frank D Sonnichsen (Otto Diels Institute for Organic Chemistry, Christian Albrechts University, Kiel, Germany) for his helpful support with respect to some of our NMR experiments. Last but not least, Dr Anna Kozarova (University of Windsor, Windsor, Ontario Canada) is highly acknowledged for critical reading and helpful comments on the manuscript. This publication acknowledges KAUST support, but has no KAUST affiliated authors.

PY - 2019/2/27

Y1 - 2019/2/27

N2 - 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.

AB - 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.

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DO - 10.1021/acsomega.8b02471

M3 - Article

SN - 2470-1343

VL - 4

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EP - 4220

JO - ACS Omega

JF - ACS Omega

IS - 2

ER -

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

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