Matrix degradability regulates NPC transcriptional activity, proliferation, and nuclear morphology. A) Schematic depicting ways in which matrix remodeling can impact NPC phenotype, highlighting that epigenetic changes and alterations in secretory phenotype remain unexplored. B) Immunofluorescence imaging of nuclei for NPCs cultured for 7 days in ELP hydrogels with varying degradability. Blue: DAPI (DNA); green: EdU; red: Sox2. NPCs cultured in high degradability gels exhibit increased fractions of nuclei that are positive for C) the stemness-associated transcription factor Sox2 and D) EdU incorporation and E) that are relatively large in size (projected nuclear area >80 μm2). Data are presented as mean ± s.d. n = 8 independent gels for Sox2 and nuclear size and 4 independent gels for EdU. *p < 0.05, ****p < 0.0001, one-way ANOVA with Bonferroni post hoc test.