Rapid and quantitative measurement of cell adhesion and migration activity by time-series analysis on biomimetic topography

Abstract

Glioblastoma Multiforme (GBM) is the most malignant brain tumor in adults, highly infiltrative and difficult to cure. According to the histopathological evidence, the glioma cells are found to infiltrate into the surround normal brain tissue, along the Scherer's structure (e.g. white matter tract and microvasculature). As a major invasion route of microenvironments, these pre-existing anatomic structures should be considered in studying infiltrative movement of glioblastoma. In our previous work, we introduced in vitro biomimetic platform as alternative model of brain-anatomical structures to study about migratory phenotypes of glioblastoma. By applying this proper biomimetic platform, we further investigated the influence of integrin, which is one of mechanoreceptors to sense mechanical cues, on phenotype of glioblastoma cells in this study. On in vitro biomimetic platform, glioblastoma cells show elongated morphology with highly aligned along the patterned direction, which is similar to that on in vivo condition. These morphological changes were gradually progressed in time-dependent manner, which might be mediated by a representative mechanoreceptor, integrin. Treatment of cell adhesive motif for integrin inhibition hinders the morphological dynamics on in vitro biomimetic platform in early time-point compared with cell proliferation cycle. Since cell adhesion mediated by mechanoreceptors is one of essential steps in migration/invasion, our results imply that effect of integrin on glioblastoma invasion is mediated by the mechanosensing process on topography and indicated by morphological changes. For further application, this quantitative analysis of glioblastoma morphology on biomimetic platform can be contributed to simple and ease investigation and effective anti-cancer drug screening.