Sulfated glycopeptide nanostructures for multipotent protein activation

Sungsoo S. Lee; Timmy Fyrner; Feng Chen; Zaida Álvarez; Eduard Sleep; Danielle S. Chun; Joseph A. Weiner; Ralph W. Cook; Ryan D. Freshman; Michael S. Schallmo; Karina M. Katchko; Andrew D. Schneider; Justin T. Smith; Chawon Yun; Gurmit Singh; Sohaib Z. Hashmi; Mark T. McClendon; Zhilin Yu; Stuart R. Stock; Wellington K. Hsu; Erin L. Hsu; Samuel I. Stupp

doi:10.1038/nnano.2017.109

Sulfated glycopeptide nanostructures for multipotent protein activation

Sungsoo S. Lee, Timmy Fyrner, Feng Chen, Zaida Álvarez, Eduard Sleep, Danielle S. Chun, Joseph A. Weiner, Ralph W. Cook, Ryan D. Freshman, Michael S. Schallmo, Karina M. Katchko, Andrew D. Schneider, Justin T. Smith, Chawon Yun, Gurmit Singh, Sohaib Z. Hashmi, Mark T. McClendon, Zhilin Yu, Stuart R. Stock, Wellington K. HsuErin L. Hsu, Samuel I. Stupp^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

162 Scopus citations

Abstract

Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.

Original language	English (US)
Pages (from-to)	821-829
Number of pages	9
Journal	Nature nanotechnology
Volume	12
Issue number	8
DOIs	https://doi.org/10.1038/nnano.2017.109
State	Published - Aug 1 2017

Funding

The NIH National Institute of Dental and Craniofacial Research grant 5R01DE015920-10, and also by the Louis A. Simpson & KimberlyQuerrey Center for Regenerative Nanomedicine at Northwestern University. The synthesis and structural characterization of this work was supported by the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by DOE, Office of Science, Basic Energy Sciences, under award no. DE-SC0000989. Studies on the dynamics and X-ray scattering were supported by the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, under award no. DE-FG02-00ER45810. The SAXS experiments were performed at the DND-CAT located at Sector 5 of the Advanced Photon Source (APS). Synchrotron X-ray ìCT experiments were performed at Sector 2-BM of the APS.We thank the following facilities at Northwestern University: Analytical BioNanotechnology Equipment Core, Peptide Synthesis Core, Center for Advanced Microscopy, Biological Imaging Facility, Keck Biophysics Facility, Integrated Molecular Structure Education and Research Center, Quantitative Bio-element Imaging Center, Center for Advanced Molecular Imaging, and Research Histology and Phenotyping Laboratory.

ASJC Scopus subject areas

Condensed Matter Physics
Bioengineering
Atomic and Molecular Physics, and Optics
Electrical and Electronic Engineering
Biomedical Engineering
General Materials Science

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10.1038/nnano.2017.109

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Lee, S. S., Fyrner, T., Chen, F., Álvarez, Z., Sleep, E., Chun, D. S., Weiner, J. A., Cook, R. W., Freshman, R. D., Schallmo, M. S., Katchko, K. M., Schneider, A. D., Smith, J. T., Yun, C., Singh, G., Hashmi, S. Z., McClendon, M. T., Yu, Z., Stock, S. R., ... Stupp, S. I. (2017). Sulfated glycopeptide nanostructures for multipotent protein activation. Nature nanotechnology, 12(8), 821-829. https://doi.org/10.1038/nnano.2017.109

@article{fa9481f926de49139c26bd027b915316,

title = "Sulfated glycopeptide nanostructures for multipotent protein activation",

abstract = "Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.",

author = "Lee, \{Sungsoo S.\} and Timmy Fyrner and Feng Chen and Zaida {\'A}lvarez and Eduard Sleep and Chun, \{Danielle S.\} and Weiner, \{Joseph A.\} and Cook, \{Ralph W.\} and Freshman, \{Ryan D.\} and Schallmo, \{Michael S.\} and Katchko, \{Karina M.\} and Schneider, \{Andrew D.\} and Smith, \{Justin T.\} and Chawon Yun and Gurmit Singh and Hashmi, \{Sohaib Z.\} and McClendon, \{Mark T.\} and Zhilin Yu and Stock, \{Stuart R.\} and Hsu, \{Wellington K.\} and Hsu, \{Erin L.\} and Stupp, \{Samuel I.\}",

note = "Funding Information: The NIH National Institute of Dental and Craniofacial Research grant 5R01DE015920-10, and also by the Louis A. Simpson \& KimberlyQuerrey Center for Regenerative Nanomedicine at Northwestern University. The synthesis and structural characterization of this work was supported by the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by DOE, Office of Science, Basic Energy Sciences, under award no. DE-SC0000989. Studies on the dynamics and X-ray scattering were supported by the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, under award no. DE-FG02-00ER45810. The SAXS experiments were performed at the DND-CAT located at Sector 5 of the Advanced Photon Source (APS). Synchrotron X-ray ?CT experiments were performed at Sector 2-BM of the APS.We thank the following facilities at Northwestern University: Analytical BioNanotechnology Equipment Core, Peptide Synthesis Core, Center for Advanced Microscopy, Biological Imaging Facility, Keck Biophysics Facility, Integrated Molecular Structure Education and Research Center, Quantitative Bio-element Imaging Center, Center for Advanced Molecular Imaging, and Research Histology and Phenotyping Laboratory. Publisher Copyright: {\textcopyright} 2017 Macmillan Publishers Limite.",

year = "2017",

month = aug,

day = "1",

doi = "10.1038/nnano.2017.109",

language = "English (US)",

volume = "12",

pages = "821--829",

journal = "Nature nanotechnology",

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Lee, SS, Fyrner, T, Chen, F, Álvarez, Z, Sleep, E, Chun, DS, Weiner, JA, Cook, RW, Freshman, RD, Schallmo, MS, Katchko, KM, Schneider, AD, Smith, JT, Yun, C, Singh, G, Hashmi, SZ, McClendon, MT, Yu, Z, Stock, SR , Hsu, WK , Hsu, EL & Stupp, SI 2017, 'Sulfated glycopeptide nanostructures for multipotent protein activation', Nature nanotechnology, vol. 12, no. 8, pp. 821-829. https://doi.org/10.1038/nnano.2017.109

TY - JOUR

T1 - Sulfated glycopeptide nanostructures for multipotent protein activation

AU - Lee, Sungsoo S.

AU - Fyrner, Timmy

AU - Chen, Feng

AU - Álvarez, Zaida

AU - Sleep, Eduard

AU - Chun, Danielle S.

AU - Weiner, Joseph A.

AU - Cook, Ralph W.

AU - Freshman, Ryan D.

AU - Schallmo, Michael S.

AU - Katchko, Karina M.

AU - Schneider, Andrew D.

AU - Smith, Justin T.

AU - Yun, Chawon

AU - Singh, Gurmit

AU - Hashmi, Sohaib Z.

AU - McClendon, Mark T.

AU - Yu, Zhilin

AU - Stock, Stuart R.

AU - Hsu, Wellington K.

AU - Hsu, Erin L.

AU - Stupp, Samuel I.

N1 - Funding Information: The NIH National Institute of Dental and Craniofacial Research grant 5R01DE015920-10, and also by the Louis A. Simpson & KimberlyQuerrey Center for Regenerative Nanomedicine at Northwestern University. The synthesis and structural characterization of this work was supported by the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by DOE, Office of Science, Basic Energy Sciences, under award no. DE-SC0000989. Studies on the dynamics and X-ray scattering were supported by the US Department of Energy (DOE), Office of Science, Office of Basic Energy Sciences, under award no. DE-FG02-00ER45810. The SAXS experiments were performed at the DND-CAT located at Sector 5 of the Advanced Photon Source (APS). Synchrotron X-ray ?CT experiments were performed at Sector 2-BM of the APS.We thank the following facilities at Northwestern University: Analytical BioNanotechnology Equipment Core, Peptide Synthesis Core, Center for Advanced Microscopy, Biological Imaging Facility, Keck Biophysics Facility, Integrated Molecular Structure Education and Research Center, Quantitative Bio-element Imaging Center, Center for Advanced Molecular Imaging, and Research Histology and Phenotyping Laboratory. Publisher Copyright: © 2017 Macmillan Publishers Limite.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.

AB - Biological systems have evolved to utilize numerous proteins with capacity to bind polysaccharides for the purpose of optimizing their function. A well-known subset of these proteins with binding domains for the highly diverse sulfated polysaccharides are important growth factors involved in biological development and tissue repair. We report here on supramolecular sulfated glycopeptide nanostructures, which display a trisulfated monosaccharide on their surfaces and bind five critical proteins with different polysaccharide-binding domains. Binding does not disrupt the filamentous shape of the nanostructures or their internal β-sheet backbone, but must involve accessible adaptive configurations to interact with such different proteins. The glycopeptide nanostructures amplified signalling of bone morphogenetic protein 2 significantly more than the natural sulfated polysaccharide heparin, and promoted regeneration of bone in the spine with a protein dose that is 100-fold lower than that required in the animal model. These highly bioactive nanostructures may enable many therapies in the future involving proteins.

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Sulfated glycopeptide nanostructures for multipotent protein activation

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