Abstract
This work investigates the mechano-biological features of cells cultured in monolayers in response to different osmotic conditions. In-vitro experiments have been performed to quantify the long-term effects of prolonged osmotic stresses on the morphology and proliferation capacity of glioblastoma cells. The experimental results highlight that both hypotonic and hypertonic conditions affect the proliferative rate of glioblastoma cells on different cell cycle phases. Moreover, glioblastoma cells in hypertonic conditions display a flattened and elongated shape. The latter effect is explained using a nonlinear elastic model for the single cell. Due to a crossover between the free energy contributions related to the cytosol and the cytoskeletal fibers, a critical osmotic stress determines a morphological transition from a uniformly compressed to an elongated shape.
Highlights
Glioblastoma is the most common and aggressive adult glioma
Glioblastoma Multiforme (GBM) is one of the most common and aggressive tumors and practically impossible to treat due to its high invasive and infiltrative growth, despite the great progress made in the last decades for the development of new imaging techniques for brain tumours and for genetic targeting of adjuvant therapies
Our results suggest the micro–environment is a key factor in GBM development owing to the mutual chemo-mechanical feedback exchanged with the tumour
Summary
Glioblastoma (or glioblastoma multiforme, GBM) is the most common and aggressive adult glioma. The GBM arises from astrocytes, the most abundant category of glial cells and almost half of the cells contained in the brain glia. Within the GBM group it is possible to pinpoint two categories on the base of the clinical appearance: the primary and secondary glioblastoma subtypes. A GBM is defined primary (approximately 90%) if it develops rapidly de novo in elderly patients, without clinical or histologic evidence of a less malignant precursor lesion; in this case, patients have symptoms less than six months prior to diagnosis. A GBM is defined secondary when it progresses from low-grade diffuse astrocytoma or anaplastic astrocytoma and generally it develops in younger patients with signs and/or symptoms for longer than six months and carries a significant better prognosis. Primary and secondary glioblastomas are indistinguishable, but they differ in their genetic and epigenetic profiles [2]
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