# Tunable hydrogel viscoelasticity modulates human neural maturation

## TL;DR

This study shows that the viscoelastic properties of a hydrogel environment can influence the maturation of human neural cells in a lab setting.

## Contribution

The paper introduces tunable protein-engineered hydrogels that mimic brain ECM viscoelasticity to modulate human neural progenitor maturation.

## Key findings

- NPCs in hydrogels with faster stress relaxation rates showed longer neuritic projections and higher neural maturation gene expression.
- Inhibiting actin polymerization reduced neuritic projections and maturation gene expression.
- Viscoelastic microenvironments can bias human NPC maturation phenotypes.

## Abstract

Human-induced pluripotent stem cells (hiPSCs) have emerged as a promising in vitro model system for studying neurodevelopment. However, current models remain limited in their ability to incorporate tunable biomechanical signaling cues imparted by the extracellular matrix (ECM). The native brain ECM is viscoelastic and stress-relaxing, exhibiting a time-dependent response to an applied force. To recapitulate the remodelability of the neural ECM, we developed a family of protein-engineered hydrogels that exhibit tunable stress relaxation rates. hiPSC-derived neural progenitor cells (NPCs) encapsulated within these gels underwent relaxation rate-dependent maturation. Specifically, NPCs within hydrogels with faster stress relaxation rates extended longer, more complex neuritic projections, exhibited decreased metabolic activity, and expressed higher levels of genes associated with neural maturation. By inhibiting actin polymerization, we observed decreased neuritic projections and a concomitant decrease in neural maturation gene expression. Together, these results suggest that microenvironmental viscoelasticity is sufficient to bias human NPC maturation.

Human neural progenitor cells exhibit distinct maturation phenotypes as a result of the viscoelasticity of their microenvironment.