The neurotransmitter glutamate modulates collective cell dynamics and calcium signaling during Isotropic–Nematic–Jamming transitions in glioma cancer cells, behaving as an active liquid crystal

Collective cell migration exhibits emergent dynamics analogous to active matter and is fundamental to tissue morphogenesis, wound healing, and cancer invasion. While isotropic, nematic, and jammed phase transitions regulate these behaviors, the influence of neurochemical signaling remains underexplored. Here, we quantitatively investigate how glutamate signaling—a neurotransmitter and glioma autocrine/paracrine factor—modulates collective dynamics and phase transitions in NPA-GCaMP6f glioma cell monolayers over 80 hours in vitro. Using high-resolution time-lapse imaging, automated tracking, and clustering, we analyzed transitions across isotropic, nematic, and jammed regimes under control and glutamate conditions. Glutamate exposure significantly increased migration velocity, spatial coverage, and aspect ratio during the nematic phase, and raised proliferation by 47% during jamming. Glutamate also reduced half-integer topological defect density and altered calcium excitability, with PIEZO1 redistributing from the membrane to the nuclear envelope—suggesting crosstalk between mechanosensitive and glutamatergic pathways. Neurochemical cues can reshape the organization and behavior of cell populations, offering new insights into how tumor progression is governed by both signaling and physical principles. This research bridges physics and biology, providing quantitative insight into how signaling regulates active matter dynamics.