Quantification of intercellular adhesion forces measured by fluid force microscopy

The mechanics of cancer cell adhesion to its neighboring cells, homotypic or heterotypic, have significant impact on tumor progression and metastasis. Intercellular adhesion has been quantified previously using atomic force microscopy-based methods. Here we show the feasibility of the recently developed fluidic force microscopy (FluidFM) to measure adhesive forces exerted by breast cancer cells. Multiple cell pairs were assessed at precisely controlled, increasing contact durations by pressure-dependent immobilization of a cell at the probe tip. Eliminating chemical fixation of the cell at the tip ensured repeated use of the same probe and also minimized changes in cell physiology. Our data indicates distinct trends of adhesion forces between homotypic breast cancer cells compared to heterotypic adhesion between cancer-fibroblast and cancer-epithelial cell pairs. Adhesion forces were similar for all three cell pairs at short contact duration (< 1 min) but differed at longer contact period (30 min). Our study suggests that FluidFM is a rapid efficient technique that could be used to assess heterogeneity in cellular adhesion at various stages of malignant transformation.