Comparing quantitative phase derived cellular mechanical parameters with atomic force microscopy measurements (Conference Presentation)

Abstract

Cellular viscoelasticity is a biomarker for cancer type and toxin exposure. Current standard methods for probing cellular stiffness are slow, laborious, and utilize complex or indirect detection. These limitations prevent effective study of changes to viscoelasticity over time as well as longitudinal study of single cells. To enable direct and non-contact measurement of stiffness, we developed a quantitative phase imaging (QPI) based method to directly measure mechanical displacement in living cells in response to static loading. We calculated mechanical parameters, including shear stiffness, to discriminate between different cancer types and cell types that were exposed to varied levels of environmental and pharmacological toxins. We also demonstrated a correlation between our shear stiffness parameter and disorder strength, a measure of cellular refractive index homogeneity acquired via a single QPI image, showing the feasibility of high-throughput, nondestructive mechanical measurements. Now, we compare our methods to atomic force microscopy (AFM), the gold standard for measuring cellular viscoelastic characteristics. We evaluate multiple breast cancer cell lines that are dosed with varying concentrations of cytochalasin B, an actin network-disrupting toxin. Each group is characterized by a commercial AFM to measure Young’s modulus and indentation stiffness. The same groups are analyzed using our QPI system to simultaneously measure shear stiffness and disorder strength. Relationships between all four measurements are analyzed to determine the correlation between the QPI derived parameters and those found using the commercial AFM, and to explore the feasibility of using QPI as a high-throughput alternative to AFM for measurements of cellular viscoelasticity.