AFM-based analysis of human metastatic cancer cells

TLDR

Biomarkers of cancer cell biomechanics, particularly stiffness, have been recognized as critical to cell function and invasion, a concept first highlighted in our 2007 study. The study reports on the biophysical properties of patient‑derived effusion cells and investigates how cell morphology affects measured stiffness. Atomic force microscopy was employed to assess the nanomechanical responses of metastatic cancer cells and benign mesothelial cells obtained from human body cavity fluids. Metastatic tumor cells were found to be over 80 % softer than benign cells, with a much narrower stiffness distribution and about 33 % lower surface adhesion, showing that morphology alone does not explain the elastic differences and suggesting that biomechanical profiling could enhance cancer diagnosis.

Abstract

Recently biomechanics of cancer cells, in particular stiffness or elasticity, has been identified as an important factor relating to cancer cell function, adherence, motility, transformation and invasion. We report on the nanomechanical responses of metastatic cancer cells and benign mesothelial cells taken from human body cavity fluids using atomic force microscopy. Following our initial study (Cross et al 2007 Nat. Nanotechnol. 2 780-3), we report on the biophysical properties of patient-derived effusion cells and address the influence of cell morphology on measured cell stiffness. Using a cytocentrifugation method, which yields morphologically indistinguishable cells that can be prepared in 1 min and avoids any possible artifacts due to 12 h ex vivo culture, we find that metastatic tumor cells are more than 80% softer than benign cells with a distribution over six times narrower than that of normal cells. Consistent with our previous study, which yielded distinguishable cell populations based on ex vivo growth and morphological characteristics, our results show it is unlikely that morphology alone is sufficient to explain the difference in elastic moduli for these two cell types. Moreover, analysis of non-specific cell adhesion inherent to tumor and normal cells collected from patients show surface adhesion of tumor cells is ∼33% less adhesive compared to that of normal cells. Our findings indicate that biomechanical-based functional analysis may provide an additional platform for cytological evaluation and diagnosis of cancer in the future.