(B-75) Single-Cell Fluidic Force Spectroscopy Show Breast Cancer Cells Soften into Metastasis

Introduction:: Within a tumor, as cancer cells transition into malignancy, progressive perturbations in tissue architecture culminate in the formation of circulating tumor cells (CTCs) - cells that disseminate from primary sites and spread disease into distant locations. The degree of cancer cell invasiveness significantly impacts its mechanical properties, mainly adhesion, stiffness, and viscoelasticity. It will subsequently regulate the ability of a cell to detach and form metastatic CTCs. Connexin 43 (Cx43), a gap junction protein, plays a pivotal role in corroborating breast cell motility indicators and promoting cell softness and metastasis. Understanding and quantifying these mechanical cues will give better insights into the mechanics of cancer cell metastasis.


Materials and Methods:: Herein, we upregulated and downregulated the expression of the Cx43 expression MDA-MB-231 human breast cancer cell line as a model of cancer cells with different metastatic potentials. We then used FluidFM-based Single Cell Force Spectroscopy (SCFS) to measure and compare the adhesion forces and elastic deformability in their single and monolayer cell states. We then assessed the cells’ detachment profiles and membrane viscous properties using Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D).


Results, Conclusions, and Discussions:: Our results show that MDA-MB-231 with upregulated expression of Cx43 exhibit strong intercellular adhesion forces per cell, in monolayers, with a considerably stiff phenotype, contrary to MDA-MB-231 cells with downregulated expression of Cx43. The biomechanical properties obtained are associated with the metastatic potential of these cells such that the forces of adhesion and viscoelasticity are inversely proportional to cell invasiveness. Our study demonstrates a new quantitative and real-time biomechanical insight into cancer metastasis and complements the established standard molecular analysis tools for studying cancer mechanical properties across the different metastatic stages.


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