Correlation of biomechanics and cancer cell phenotype by combined Brillouin and Raman spectroscopy of U87-MG glioblastoma cells

Abstract

The elucidation of biomechanics furthers understanding of brain tumor biology. Brillouin spectroscopy is a new optical method that addresses viscoelastic properties down to subcellular resolution in contact-free manner. Moreover, it can be combined with Raman spectroscopy to obtain co-localized biochemical information. Here, we applied co-registered Brillouin and Raman spectroscopy to U87-MG human glioblastoma cells in vitro. Using 2D and 3D cultures, we related biomechanical properties with local biochemical composition at subcellular level, as well as cell phenotype. Brillouin and Raman mapping of adherent cells showed that the nucleus and nucleoli are stiffer than the perinuclear region and the cytoplasm. The biomechanics of cell cytoplasm is affected by culturing conditions, i.e. cells grown as spheroids being stiffer than adherent cells. Inside the spheroids, the presence of lipid droplets as assessed by Raman spectroscopy reveals higher Brillouin shifts which is not related to local stiffness increase, but due to a higher refractive index combined with a lower mass density. This highlights the importance of locally defined biochemical reference data for a correct interpretation of the Brillouin shift of cells and tissue in future studies investigating the biomechanics of brain tumor models by Brillouin spectroscopy.