Cell Trapping via Migratory Inhibition within Density-Tuned Electrospun Nanofibers.

Abstract

Cell migration is an essential bioprocess that occurs during wound healing and tissue regeneration. Abnormal cell migration is observed in various pathologies, including cancer metastasis. Glioblastoma multiforme (GBM) is an aggressive and highly infiltrative brain tumor. The white matter tracts are considered the preferred routes for GBM invasion and the subsequent spread throughout the brain tissue. In the present study, a platform based on electrospun nanofibers with a consistent alignment and controlled density was designed to inhibit cell migration. The observation of the cells cultured on the nanofibers with different fiber densities revealed an inverse correlation between the cell migration velocity and nanofiber density. This was attributed to the formation of focal adhesions (FAs). The FAs in the sparse fiber matrix were small, whereas those in the dense fiber matrix were large, aligned with the nanofibers, and distributed throughout the cells. A nanofiber-based platform with stepwise different fiber densities was designed based on the aforementioned observation. A time-lapse observation of the GBM cells cultured on the platform revealed a directional one-way migration that induced the entrapment of cells in the dense-fiber zone. The designed platform mimicked the structure of the white matter tracts and enabled the entrapment of migrating cells. The demonstrated approach is suitable for inhibiting metastasis and understanding the biology of invasion, thereby functioning as a promising therapeutic strategy for GBM.