Culturing astrocytes on substrates that mimic brain tumors promotes enhanced mechanical forces

Abstract

Astrocytes are essential to brain homeostasis and their dysfunction can have devastating consequences on human quality of life. Such deleterious effects are generally due in part to changes that occur at the cellular level, which may be biochemical or biomechanical in nature. One biomechanical change that can occur is a change in tissue stiffness. Brain tumors are generally associated with increased brain tissue stiffness, but the impact increased tissue stiffness has on astrocyte biomechanical behavior is poorly understood. Therefore, in this study we cultured human astrocytes on flexible substrates with stiffness that mimicked the healthy human brain (1 kPa), meningioma (4 kPa), and glioma (11 kPa) and investigated astrocyte biomechanical behavior by measuring cell-substrate tractions, strain energies, cell-cell intercellular stresses, and cellular velocities. In general, tractions, intercellular stresses, and strain energy was observed to increase as a function of increased substrate stiffness, while cell velocities were observed to decrease with increased substrate stiffness. We believe this study will be of great importance to the fields of brain pathology and brain physiology.

Keywords: Astrocytes; Biomechanics; Brain tumors; Extracellular matrix; Stiffness.