Nanomechanical Signatures in Glioma Cells Depend on CD44 Distribution in IDH1 Wild-Type but Not in IDH1R132H Mutant Early-Passage Cultures

Atomic force microscopy (AFM) recently burst into biomedicine, providing morphological and functional characteristics of cancer cells and their microenvironment responsible for tumor invasion and progression, although the novelty of this assay needs to coordinate the malignant profiles of patients' specimens to diagnostically valuable criteria. Applying high-resolution semi-contact AFM mapping on an extended number of cells, we analyzed the nanomechanical properties of glioma early-passage cell cultures with a different IDH1 R132H mutation status. Each cell culture was additionally clustered on CD44+/- cells to find possible nanomechanical signatures that differentiate cell phenotypes varying in proliferative activity and the characteristic surface marker. IDH1 R132H mutant cells compared to IDH1 wild-type ones (IDH1wt) characterized by two-fold increased stiffness and 1.5-fold elasticity modulus. CD44+/IDH1wt cells were two-fold more rigid and much stiffer than CD44-/IDH1wt ones. In contrast to IDH1 wild-type cells, CD44+/IDH1 R132H and CD44-/IDH1 R132H did not exhibit nanomechanical signatures providing statistically valuable differentiation of these subpopulations. The median stiffness depends on glioma cell types and decreases according to the following manner: IDH1 R132H mt (4.7 mN/m), CD44+/IDH1wt (3.7 mN/m), CD44-/IDH1wt (2.5 mN/m). This indicates that the quantitative nanomechanical mapping would be a promising assay for the quick cell population analysis suitable for detailed diagnostics and personalized treatment of glioma forms.

Automated summary

Atomic force microscopy (AFM) has recently become a valuable tool in biomedicine, allowing for the analysis of cancer cells and their microenvironment to better understand tumor invasion and progression. In this study, high-resolution AFM mapping was used to analyze the nanomechanical properties of glioma cell cultures with different IDH1 R132H mutation statuses. The results showed that IDH1 R132H mutant cells exhibited increased stiffness and elasticity modulus compared to IDH1 wild-type cells. Additionally, CD44+/IDH1wt cells were found to be more rigid and stiffer than CD44-/IDH1wt cells. However, there were no significant nanomechanical differences between CD44+/IDH1 R132H and CD44-/IDH1 R132H cells. These findings suggest that quantitative nanomechanical mapping holds promise for the accurate analysis of cell populations and personalized treatment of glioma.