Matrix Stiffness Regulates GBM Migration and Chemoradiotherapy Responses via Chromatin Condensation in 3D Viscoelastic Matrices

• DOI: 10.1021/acsami.4c16993
• Publication Date: 2025-02-06T15:08:12Z
• Authors: Sauradeep Sinha; Mark Fleck; Manish Ayushman; Xinming Tong; Georgios Mikos; Sarah Jones; Luis Soto; Fan Yang
• Keywords: Matrix (chemical analysis)

Glioblastoma multiforme (GBM) progression is associated with changes in matrix stiffness, and different regions of the tumor niche exhibit distinct stiffnesses. Using elastic hydrogels, previous work has demonstrated that stiffness modulates GBM behavior drug responses. However, brain tissue viscoelastic, how impacts invasive phenotype response to therapy within a viscoelastic remains largely unclear. Here, we report three-dimensional (3D) hydrogel system models heterogeneity present niche. We find cells enhanced migratory ability, proliferation, resistance radiation soft matrices, mimicking core perifocal margins. Conversely, remain confined demonstrate increased chemotherapy stiff matrices edematous regions. identify stiffness-induced are regulated by nuclear mechanosensing chromatin condensation. Pharmacologically decondensing significantly impedes migration overcomes chemoresistance radioresistance. Our findings highlight regulates aggressive through mechanotransduction processes. Finally, reveal critical role condensation mediating resistance, offering potential new therapeutic target improve treatment outcomes.