Investigation of Adhesion and Mechanical Properties of Human Glioma Cells by Single Cell Force Spectroscopy and Atomic Force Microscopy

Abstract

Active cell migration and invasion is a peculiar feature of glioma that makes this tumor able to rapidly infiltrate into the surrounding brain tissue. In our recent work, we identified a novel class of glioma-associated-stem cells (defined as GASC for high-grade glioma -HG- and Gasc for low-grade glioma -LG-) that, although not tumorigenic, act supporting the biological aggressiveness of glioma-initiating stem cells (defined as GSC for HG and Gsc for LG) favoring also their motility. Migrating cancer cells undergo considerable molecular and cellular changes by remodeling their cytoskeleton and cell interactions with surrounding environment. To get a better understanding about the role of the glioma-associated-stem cells in tumor progression, cell deformability and interactions between glioma-initiating stem cells and glioma-associated-stem cells were investigated. Adhesion of HG/LG-cancer cells on HG/LG-glioma-associated stem cells was studied by time-lapse microscopy, while cell deformability and cell-cell adhesion strengths were quantified by indentation measurements by atomic force microscopy and single cell force spectroscopy. Our results demonstrate that for both HG and LG glioma, cancer-initiating-stem cells are softer than glioma-associated-stem cells, in agreement with their neoplastic features. The adhesion strength of GSC on GASC appears to be significantly lower than that observed for Gsc on Gasc. Whereas, GSC spread and firmly adhere on Gasc with an adhesion strength increased as compared to that obtained on GASC. These findings highlight that the grade of glioma-associated-stem cells plays an important role in modulating cancer cell adhesion, which could affect glioma cell migration, invasion and thus cancer aggressiveness. Moreover this work provides evidence about the importance of investigating cell adhesion and elasticity for new developments in disease diagnostics and therapeutics.

Nanoscale adhesion forces between the fungal pathogen Candida albicans and macrophages

“…2c shows a typical force-distance signature obtained upon separating C. albicans-macrophage interacting cells. It is worth noting that while yeast cells are much smaller than mammalian cells, the work of adhesion estimated here is in the range of that described between animal cells, 24,40,41 suggesting that multiple biomolecular bonds are involved and that the intercellular contact area is large due to the deformable macrophage membrane. 22,24 The maximum adhesion force (F adh ), generally occurring at a short distance, represents the rupture of specific and unspecific cell-cell interactions.…”

Quantifying cellular mechanics and adhesion in renal tubular injury using single cell force spectroscopy

“…The importance of characterising both elasticity and adhesion strength using AFM based SCFS was recently highlighted by Andolfi et al 28 in cancer migration. In the current study,…”

Quantitative characterization of single‐cell adhesion properties by atomic force microscopy using protein‐functionalized microbeads

“…By determining the proportion of attached cells remaining on a substrate after several washing steps, nonadhesive or weakly adhesive and adhesive cell subpopulations can be separated, but the adhesion properties of cells within the adhesive group remain out of reach. On the other hand, AFM uses a controlled detachment force in a single‐cell approach to quantify the interactions between the individual cell and a substrate, such as ECM proteins or another cell . AFM thus allows for a reproducible, quantitative, and discriminative investigation of the adhesive properties of adherent cells in common cell culture conditions.…”