Total variation of quantitative phase map reveals cellular Young's modulus

Collective cell migration is a fundamental physiological process involved in wound healing, development, and tissue regeneration. Though the role of the environmental stiffness in collective cell migration has been extensively investigated, the effects of cellular stiffness have been less studied due to the lack of high-throughput in situ methods for characterizing cellular stiffness. Here, we characterize the cellular Youngs modulus in situ with a large field of view and in real time using use quantitative phase microscopy. We found that standard deviation and total variation of the phase are inversely related to the cellular Youngs modulus, while the total variation of phase has finer mechanical resolution. Integrating the total variation of phase with cell segmentation algorithms, we efficiently analyzed the cellular Youngs modulus for cells in a monolayer. Using this system, we found the cells at the wound frontier are much softer than that of the cells in the inner region of monolayer in in vitro wound healing assay. At single cellular level, the Youngs modulus of leader cells, boundary cells, and inner cells are significantly distinct from each other. To conclude, our method would help elucidate the essential role of cellular stiffness in collective cell migration and has the potential to further benefit the progress of mechanobiology.