Supramolecular Nanostructure Activates TrkB Receptor Signaling of Neuronal Cells by Mimicking Brain-Derived Neurotrophic Factor
Open accessAbstract
Brain-derived neurotrophic factor (BDNF), a neurotrophin that binds specifically to the tyrosine kinase B (TrkB) receptor, has been shown to promote neuronal differentiation, maturation, and synaptic plasticity in the central nervous system (CNS) during development or after injury and onset of disease. Unfortunately, native BDNF protein-based therapies have had little clinical success due to their suboptimal pharmacological properties. In the past 20 years, BDNF mimetic peptides have been designed with the purpose of activating certain cell pathways that mimic the functional activity of native BDNF, but the interaction of mimetic peptides with cells can be limited due to the conformational specificity required for receptor activation. We report here on the incorporation of a BDNF mimetic sequence into a supramolecular peptide amphiphile filamentous nanostructure capable of activating the BDNF receptor TrkB and downstream signaling in primary cortical neurons in vitro. Interestingly, we found that this BDNF mimetic peptide is only active when displayed on a peptide amphiphile supramolecular nanostructure. We confirmed that increased neuronal maturation is linked to TrkB signaling pathways by analyzing the phosphorylation of downstream signaling effectors and tracking electrical activity over time. Furthermore, three-dimensional gels containing the BDNF peptide amphiphile (PA) nanostructures encourage cell infiltration while increasing functional maturation. Our findings suggest that the BDNF mimetic PA nanostructure creates a highly bioactive matrix that could serve as a biomaterial therapy in injured regions of the CNS. This new strategy has the potential to induce endogenous cell infiltration and promote functional neuronal maturation through the presentation of the BDNF mimetic signal.
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Display of BDNF on the peptide amphiphile is necessary for this effect to be observed.
“Display of BDNF on the peptide amphiphile is necessary for this effect to be observed199.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [199]
The peptides contain brain-derived neurotrophic factor (BDNF), which enables the formation of mature neurons via activation of the TrkB pathway.
“The peptides contain brain-derived neurotrophic factor (BDNF), which enables the formation of mature neurons via activation of the TrkB pathway.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [199]
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Towards organoid culture without Matrigel
Kozlowski, M. T., Crook, C. J., & Ku, H. T. (2021) · Communications Biology · doi:10.1038/s42003-021-02910-8 · Cited by 409 · see citing works
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- Authors
- Edelbrock, A. N., Àlvarez, Z., Simkin, D., Fyrner, T., Chin, S. M., Sato, K., Kiskinis, E., & Stupp, S. I.
- Affiliations
- Northwestern University (US)
- Simpson Querrey Institute, Northwestern University, Chicago, Illinois 60611, United States
- Corresponding author
- Stupp, Samuel I.
- ORCID
- Venue
- Nano Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-09-13
- Volume
- 18
- Issue
- 10
- Pages
- 6237-6247
- ISSN
- 1530-6984 (ISSN-L)
- 1530-6992
- PMC
- PMC6207372
- OpenAlex
- W2891164395
- Cited by
- 103
- References
- 76
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 6 · 2023: 18 · 2022: 14 · 2021: 15 · 2020: 14 · 2019: 16 · 2018: 2
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nano Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Tokyo Tech Research Repository (Tokyo Institute of Technology) (submittedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS104219)
- Ag?ncia de Gesti? d?Ajuts Universitaris i de Recerca (2014 BP-A 00007)
- Les Turner ALS Foundation
- National Institute of Biomedical Imaging and Bioengineering (5R01EB003806-07)
- Paralyzed Veterans of America Research Foundation (PVA17_RF_0008)
- Dravet Syndrome Foundation
- Muscular Dystrophy Association
- National Science Foundation
- Louis A. Simpson and Kimberly K. Querrey Center for Regenerative Nanomedicine, Northwestern University
- Topics
- Physical Sciences › Materials Science › Biomaterials › Supramolecular Self-Assembly in Materials
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Keywords
- brain-derived neurotrophic factor, TrkB receptor, supramolecular nanostructures, neuronal maturation, cortical neurons, neurotrophin signaling, central nervous system injury, cell infiltration, electrical activity
- MeSH terms
- Animals, Cell Differentiation, Central Nervous System, Humans, Neuronal Plasticity, Neurons, Peptides, Phosphorylation, Signal Transduction, Brain-Derived Neurotrophic Factor, Receptor, trkB, Biomimetics, Nanostructures, Mice, Neurogenesis, Primary Cell Culture
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