| Popis: |
Glioma tumor dispersion involves invading cells escaping the tumor bulk and migrating into the healthy brain parenchyma. Here, they encounter linearly aligned track-like tissue structures such as axon bundles and the perivascular space. These environments also contain micrometer-scale pores that impose mechanical confinement on invading cells. To study glioma cell migration in anin vitrosystem that reproduces some of these features, we used microfluidic devices with 60 μm2cross-sectional area channels that confine cells into one-dimensional (1D) tracks. Individual cell tracking revealed strongly persistent migration at a mean rate of 8.5 ± 0.33 nm s-1. Notably, a 1D computational cell migration simulator predicts migration behaviors of glioma cells without significant adjustment of parameters estimated from previous experiments on two-dimensional (2D) substrates. Pharmacological inhibitors of integrin-mediated adhesions, myosin II activation, or drugs targeting F-actin assembly or microtubule dynamics influence migration consistent with simulations where relevant parameters are changed. These results suggest that cell parameters calibrated to a motor-clutch model on 2D substrates effectively predict 1D confined migration behaviorsa priori. Our results outline a method for testing biophysical mechanisms of tumor cell migration in confined spaces and predicting the effects of anti-motility therapy. |
