Dermal fibroblasts and breast cancer cells differentially alter their local stiffness landscape

Bulk measurements of ECM stiffness are commonly used in mechanobiology. However, peri-cellular stiffness can be quite heterogenous and divergent from the bulk properties. Here, we use optical tweezers active microrheology (AMR) to quantify how dermal fibroblasts (DFs) and human breast cancer cells MDA-MB-231 (MDAs) embedded in 1.0 and 1.5 mg/ml type 1 collagen (T1C) hydrogels establish dissimilar patterns of peri-cellular stiffness. We found that DFs increase local stiffness of 1.0 mg/ml T1C hydrogels, but surprisingly do not change the stiffness of 1.5 mg/ml T1C hydrogels. In contrast, MDAs largely do not alter stiffness of T1C hydrogels, as compared to cell-free controls. Results suggest that MDAs adapt to the bulk ECM stiffness, while DFs regulate local stiffness to levels they intrinsically “favor”. Further, cells were subjected to treatments that were previously shown to regulate migration, proliferation and contractility of DFs and MDAs. Following treatment, cells established different levels of stiffness magnitude and anisotropy, which were dependent on the cell line, T1C concentration and treatment. In summary, our findings demonstrate that AMR reveals otherwise masked mechanical properties such as spatial gradients and anisotropy.