Correlation Between Extracellular Matrix Stiffness, Intracellular Viscoelastic Properties, and Invasive Ability of Cancer Cells

Erin L. Baker, Muhammad H. Zaman, and Roger T. Bonnecaze

Tumors exhibit elevated stiffness compared to normal tissue, and some aspects of tumor cell invasive ability are in part governed by extracellular matrix (ECM) stiffness. Yet neither the relationship between ECM stiffness and intracellular mechanical properties, nor that between intracellular mechanical properties and invasive ability, is well understood. In order to establish these relationships quantitatively, we employ particle-tracking microrheology to investigate the intracellular viscoelastic properties of single cancer cells that are attached to two-dimensional (2D) substrates, as well as those that are embedded within three-dimensional (3D) matrices. While particle-tracking rheological protocols have been established, these techniques have yet to be applied in linking the cytoplasmic mechanical environment of cancer cells to their invasive ability. Specifically, the intracellular mechanical properties of elasticity, viscosity, and compliance of human prostate cancer (PC-3) cells and transformed human breast cancer (MCF-10A) cells of varying invasive ability are extracted from Brownian motions of individual 1.0μm polystyrene spheres that are ballistically delivered to their cytoplasm. Results indicate that the cytoplasmic mechanical environment of PC-3 cells attached to a 2D substrate is non-homogenous, independent of matrix stiffness. Furthermore, the heterogeneously varying intracellular viscoelastic properties show a strong correlation with matrix chemistry and mechanical architecture. These viscoelastic properties are also shown to correlate with the invasiveness of the cancer cells.