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Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel

Sualyneth Galarza, Alfred J. Crosby, ChangHui Pak, Shelly R. Peyton
doi: https://doi.org/10.1101/785683
Sualyneth Galarza
1Department of Chemical Engineering, University of Massachusetts, Amherst MA 01003, USA
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Alfred J. Crosby
2Department of Polymer Science and Engineering, University of Massachusetts, Amherst MA 01003
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ChangHui Pak
3Department of Biochemistry and Molecular Biology University of Massachusetts, Amherst MA 01003
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Shelly R. Peyton
1Department of Chemical Engineering, University of Massachusetts, Amherst MA 01003, USA
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  • For correspondence: speyton@umass.edu
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Abstract

Bioengineers designed numerous instructive brain extracellular matrix (ECM) environments that have tailored and tunable protein composition and biomechanics in vitro to study astrocyte reactivity during trauma and inflammation. However, a major limitation of both protein-based and model microenvironments is that astrocytes within fail to retain their characteristic stellate morphology and quiescent state without becoming activated under “normal” culture conditions. Here we introduce a synthetic hydrogel, that for the first time demonstrates maintenance of astrocyte quiescence, and control over activation on demand. With this synthetic brain hydrogel, we show the brain-specific integrin-binding and matrix metalloprotease (MMP)-degradable domains of proteins control astrocyte star-shaped morphologies, and we can achieve an ECM condition that maintains astrocyte quiescence with minimal activation. In addition, we can induce activation in a dose-dependent manner via both defined cytokine cocktails and low molecular weight hyaluronic acid. We envision this synthetic brain hydrogel as a new tool to study the physiological role of astrocytes in health and disease.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted September 30, 2019.
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Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel
Sualyneth Galarza, Alfred J. Crosby, ChangHui Pak, Shelly R. Peyton
bioRxiv 785683; doi: https://doi.org/10.1101/785683
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Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel
Sualyneth Galarza, Alfred J. Crosby, ChangHui Pak, Shelly R. Peyton
bioRxiv 785683; doi: https://doi.org/10.1101/785683

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