Cancer Cells Viscoelasticity Measurement by Quantitative Phase and Flow Stress Induction

Abstract

ABSTRACTCell viscoelastic properties are affected by the cell cycle, differentiation, pathological processes such as malignant transformation. Therefore, evaluation of the mechanical properties of the cells proved to be an approach to obtaining information on the functional state of the cells. Most of the currently used methods for cell mechanophenotypisation are limited by low robustness or the need for highly expert operation. In this paper, the system and method for viscoelasticity measurement using shear stress induction by fluid flow is described and tested. Quantitative Phase Imaging (QPI) is used for image acquisition because this technique enables to quantify optical path length delays introduced by the sample, thus providing a label-free objective measure of morphology and dynamics. Viscosity and elasticity determination were refined using a new approach based on the linear system model and parametric deconvolution. The proposed method allows high-throughput measurements during live cell experiments and even through a time-lapse, where we demonstrated the possibility of simultaneous extraction of shear modulus, viscosity, cell morphology, and QPI-derived cell parameters like circularity or cell mass. Additionally, the proposed method provides a simple approach to measure cell refractive index with the same setup, which is required for reliable cell height measurement with QPI, an essential parameter for viscoelasticity calculation. Reliability of the proposed viscoelasticity measurement system was tested in several experiments including cell types of different Young/shear modulus and treatment with cytochalasin D or docetaxel, and an agreement with atomic force microscopy was observed. The applicability of the proposed approach was also confirmed by a time-lapse experiment with cytochalasin D washout, where an increase of stiffness corresponded to actin repolymerisation in time.SIGNIFICANCEWe present an approach for viscoelasticity measurement using QPI and shear stress induction by fluid flow. Our system builds and extends a recently published approach by parametric deconvolution, which allows us to eliminate the influence of the fluidic system and reliably measure both the shear modulus and viscosity of the cells in high throughput. Additionally, the proposed method enables to simultaneously determine cell refractive index map, cell dry mass map, and morphology, thereby enabling a multimodal cellular characterisation in a single measurement.