Next Article in Journal
Blockade of Intranigral and Systemic D3 Receptors Stimulates Motor Activity in the Rat Promoting a Reciprocal Interaction among Glutamate, Dopamine, and GABA
Previous Article in Journal
Pharmacokinetic Properties of Fluorescently Labelled Hydroxypropyl-Beta-Cyclodextrin
Open AccessArticle

Sustained Neurotrophin Release from Protein Nanoparticles Mediated by Matrix Metalloproteinases Induces the Alignment and Differentiation of Nerve Cells

1
Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
2
Cell Guidance Systems, Maia Building, Babraham Research Campus, Cambridge, CB22 3AT, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Biomolecules 2019, 9(10), 510; https://doi.org/10.3390/biom9100510
Received: 19 August 2019 / Revised: 17 September 2019 / Accepted: 19 September 2019 / Published: 20 September 2019
(This article belongs to the Section Biological Materials)
The spatial and temporal availability of cytokines, and the microenvironments this creates, is critical to tissue development and homeostasis. Creating concentration gradients in vitro using soluble proteins is challenging as they do not provide a self-sustainable source. To mimic the sustained cytokine secretion seen in vivo from the extracellular matrix (ECM), we encapsulated a cargo protein into insect virus-derived proteins to form nanoparticle co-crystals and studied the release of this cargo protein mediated by matrix metalloproteinase-2 (MMP-2) and MMP-8. Specifically, when nerve growth factor (NGF), a neurotrophin, was encapsulated into nanoparticles, its release was promoted by MMPs secreted by a PC12 neuronal cell line. When these NGF nanoparticles were spotted onto a cover slip to create a uniform circular field, movement and alignment of PC12 cells via their extended axons along the periphery of the NGF nanoparticle field was observed. Neural cell differentiation was confirmed by the expression of specific markers of tau, neurofilament, and GAP-43. Connections between the extended axons and the growth cones were also observed, and expression of connexin 43 was consistent with the formation of gap junctions. Extensions and connection of very fine filopodia occurred between growth cones. Our studies indicate that crystalline protein nanoparticles can be utilized to generate a highly stable cytokine gradient microenvironment that regulates the alignment and differentiation of nerve cells. This technique greatly simplifies the creation of protein concentration gradients and may lead to therapies for neuronal injuries and disease. View Full-Text
Keywords: extracellular matrix; matrix metalloproteinase; neurotrophin; NGF; PC12 cells; polyhedra; protein nanoparticles extracellular matrix; matrix metalloproteinase; neurotrophin; NGF; PC12 cells; polyhedra; protein nanoparticles
Show Figures

Figure 1

MDPI and ACS Style

Matsuzaki, Y.; Maruta, R.; Takaki, K.; Kotani, E.; Kato, Y.; Yoshimura, R.; Endo, Y.; Whitty, C.; Pernstich, C.; Gandhi, R.; Jones, M.; Mori, H. Sustained Neurotrophin Release from Protein Nanoparticles Mediated by Matrix Metalloproteinases Induces the Alignment and Differentiation of Nerve Cells. Biomolecules 2019, 9, 510.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop