PT  - JOURNAL ARTICLE
AU  - Sualyneth Galarza
AU  - Alfred J. Crosby
AU  - ChangHui Pak
AU  - Shelly R. Peyton
TI  - Control of Astrocyte Quiescence and Activation in a Synthetic Brain Hydrogel
AID  - 10.1101/785683
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 785683
4099  - http://biorxiv.org/content/early/2019/09/30/785683.short
4100  - http://biorxiv.org/content/early/2019/09/30/785683.full
AB  - 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.