The Role of Viscoelasticity in a Biomimetic Hyaluronan-Oxime Hydrogel Modelling Heterogeneous Glioblastoma Stem Cell Invasion

Abstract

The brain extracellular matrix is viscoelastic, and its role in disease cell behaviour has only begun to be understood. Glioblastoma stem cells (GSCs), as seen in the deadly brain cancer glioblastoma (GBM), are an invasive subpopulation of cells which capture the heterogeneity of GBM and are thought to drive disease progression. We developed biomimetic viscoelastic hyaluronan based hydrogels to understand the effect of viscoelasticity on the invasion of heterogeneous GSCs categorized within subgroups Reactive, Invasive, and Constructive. Hydrogel viscoelasticity was introduced through the incorporation of methyl cellulose, ECM-based proteins tenascin C and collagen IV, and hydrazone chemistry. We demonstrated that heterogeneous GSCs respond differently to viscoelasticity, with a significant increase in the invasion of Reactive GSCs in viscoelastic hydrogels. This work highlights the importance of investigating the behaviour of GSCs based on their molecular profiles and contributes to the understanding of the role of viscoelasticity in GSC invasion.

Keywords

Cell Invasion, Glioblastoma, Glioblastoma Stem Cells, Hyaluronan, Hydrogel, Viscoelasticity.