4.2 Article

Cell Trapping via Migratory Inhibition within Density-Tuned Electrospun Nanofibers

Journal

ACS APPLIED BIO MATERIALS
Volume 4, Issue 10, Pages 7456-7466

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsabm.1c00700

Keywords

migration; cell trapping; electrospinning; nanofiber; glioblastoma

Funding

  1. Terumo Life Science Foundation [19K09502, 21K09172]
  2. Japan Society for the Promotion of Science

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The study focused on cell migration inhibition by designing a nanofiber-based platform with different fiber densities, which controlled the formation of FAs and directed cell migration. The platform induced a directional one-way migration of cells leading to entrapment in specific zones, mimicking the structure of white matter tracts and offering a promising therapeutic strategy for GBM metastasis.
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.

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