Contributed Talk

Collective forces of tumor spheroids in three-dimensional biopolymer networks

Christoph Mark¹, Thomas J. Grundy², David Böhringer¹, Julian Steinwachs¹, Geraldine M. O'Neill², Ben Fabry¹

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In the pathological process of metastasis, cancer cells leave a primary tumor, either individually or collectively. This invasion process requires that cells exert physical forces onto the surrounding extracellular matrix. We describe a technique for quantifying the contractile forces that tumor spheroids collectively exert on highly nonlinear three-dimensional collagen networks. Building on an existing finite element approach for single-cell traction force microscopy [1], we exploit the spherical symmetry of tumor spheroids to derive a scale-invariant relation between spheroid contractility and the surrounding matrix deformations. The method thus avoids computationally expensive material simulations for the analysis of each individual measurement. Moreover, image acquisition can be done with low resolution (5x objective, NA=0.1) brightfield microscopy. For A172 and U87 glioblastoma spheroids, we find that the collective forces reflect the contractility of individual cells only during the initial contraction phase (≲1h), but not on longer time scales. In particular, the large strains induced by the spheroids may significantly alter the mechanical environment of the invading cells, due to strain stiffening and fiber alignment, and thus alter cellular force generation at a collective level. This new assay offers a way to investigate the mechanics behind collective effects in cancer invasion that cannot be measured on a single-cell level.