Correlating circulating tumor cells (CTCs) types with membrane viscoelasticity with atomic force microscopy

Atomic force microscopy (AFM) can measure the local cell membrane viscoelasticity of live CTCs by nano-indentations. Anecdotal observations suggest metastasized tumor cells bear phenotypical signatures in their membrane characteristics. Here, building on past work to detect and characterize CTC through a narrow passage by nano-strain interferometry, we have developed a mathematical framework to quantify cell membrane viscoelasticity by performing Ting's integral over force-distance measurements to differentiate cancer phenotypes. Five cell lines, prostate carcinoma (LNCap), adenocarcinoma (PC-3), breast carcinoma (T-47D), adenocarcinoma (MDA-MB-231), and lung carcinoma (A549) are used for this study. Differing from past studies, we probe the membrane with varying indentation depths to introduce elastic and plastic deformations. Results show distinctive hysteresis between the loading and unloading of different CTCs. It is also found that the multi-power law model is more suitable for cancer characterization. These viscoelastic measurements are used as boundary conditions in numerical simulation to study cell-flow-wall interactions in confinement.