9th Annual Symposium
Physics of Cancer
Leipzig, Germany
September 24-26, 2018
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
1Friedrich-Alexander University Erlangen-Nürnberg, Department of Physics, Biophysics group, Henkestr. 91, 91052 Erlangen, Germany
2University of Sydney, Children’s Cancer Research Unit, Focal Adhesion Biology group, Cnr Hawkesbury Rd & Hainsworth St Westmead, NSW 2145, Australia
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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.
[1]Steinwachs et al.Three-dimensional force microscopy of cells in biopolymer networks, Nature Methods (13, 2, 171-176) (2016)
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