Fingerprinting circulating tumor cells (CTCs) passing through narrow passages with membrane viscoelasticity

Atomic force microscopy (AFM) can resolve nanoscale cell surface features and perform mechanical characterization of living cells and tissues. Anecdotal observations suggest that metastasized tumor cells bear their phenotypical signatures in their membrane characteristics. In this work, we present a new methodology allowing us to quantify the mechanical properties of cells passing through narrow passage via force-deformation relations (F-D curves) by nano-indentation, as well as develop a novel mathematical framework to quantify cell membranes viscoelasticity by performing Ting's integral over F-D measurements to differentiate cancer phenotypes. We have developed a custom-made flow cell that enables simultaneous microscopic observation and AFM experimentation. Three cell lines, prostate (PC3), breast (T47D), and lung (A549) carcinomas are used for this kernel study. Gold-coated probes (k=0.03N/m) are used to allow measurements on the soft cell membrane. Differing from past studies, we probe the membrane with large indentations. Results show distinctive hysteresis between loading and unloading of the membrane. It is also found that the multi-power law model is more suitable for cancer characterization. These viscoelasticity measurements are used to inform numerical simulation to study cell-flow-wall interactions in confinement.