article published yes Zuzana Dunajova author 4B39F286-F248-11E8-B48F-1D18A9856A87 Saren Tasciyan author 4323B49C-F248-11E8-B48F-1D18A9856A870000-0003-1671-393X Juraj Majek author 3e6d9473-f38e-11ec-8ae0-c4e05a8aa9e1 Jack Merrin author 4515C308-F248-11E8-B48F-1D18A9856A870000-0001-5145-4609 Robert P. Jenkins author Erik Sahai author Michael K Sixt author 41E9FBEA-F248-11E8-B48F-1D18A9856A870000-0002-6620-9179 Edouard B Hannezo author 3A9DB764-F248-11E8-B48F-1D18A9856A870000-0001-6005-1561 EdHa department MiSi department GradSch department AnSa department NanoFab department Motile active matter models of migrating cells and chiral filaments project Pushing from within: Control of cell shape, integrity and motility by cytoskeletal pushing forces project Although studies of tumor invasion have mainly emphasized the evolution of genetic and epigenetic heterogeneity, cellular behaviors also depend on the physical microenvironment. Yet, the tumor microenvironment is both complex and continuously remodeled, making it hard to rigorously test its causal influence on tumor dissemination. Here, we adopted a reductionist approach to studying tumor cell invasion in microengineered environments of tunable patterned geometries. We find that not only the presence of obstacles but more unexpectedly their spatial disorder causes a drastic shift from a collective to a single-cell mode of invasion—comparable in strength to loss of cell-cell adhesion. Combining live-imaging and perturbation experiments with minimal biophysical modeling, we demonstrate that cell dissemination results both from local geometrical constraints and a global integration of spatial disorder over time. We identify generic universality classes of invasion dynamics dependent on environmental geometry, enabling us to identify quantitative physical principles for tumor dissemination. https://research-explorer.ista.ac.at/download/22963/23062/2026_ScienceAdv_Dunajova.pdf application/pdfno AAAS2026 eng 2375-2548 4271529810.1126/sciadv.aed0587 1237 https://research-explorer.ista.ac.at/record/21427 Z. Dunajova <i>et al.</i>, “Substrate heterogeneity promotes cancer cell dissemination through interface roughening,” <i>Science Advances</i>, vol. 12, no. 37. AAAS, 2026. Dunajova Z, Tasciyan S, Majek J, et al. Substrate heterogeneity promotes cancer cell dissemination through interface roughening. <i>Science Advances</i>. 2026;12(37). doi:<a href="https://doi.org/10.1126/sciadv.aed0587">10.1126/sciadv.aed0587</a> Dunajova, Zuzana, Saren Tasciyan, Juraj Majek, Jack Merrin, Robert P. Jenkins, Erik Sahai, Michael K Sixt, and Edouard B Hannezo. “Substrate Heterogeneity Promotes Cancer Cell Dissemination through Interface Roughening.” <i>Science Advances</i>. AAAS, 2026. <a href="https://doi.org/10.1126/sciadv.aed0587">https://doi.org/10.1126/sciadv.aed0587</a>. Dunajova Z, Tasciyan S, Majek J, Merrin J, Jenkins RP, Sahai E, Sixt MK, Hannezo EB. 2026. Substrate heterogeneity promotes cancer cell dissemination through interface roughening. Science Advances. 12(37), eaed0587. Dunajova, Z., Tasciyan, S., Majek, J., Merrin, J., Jenkins, R. P., Sahai, E., … Hannezo, E. B. (2026). Substrate heterogeneity promotes cancer cell dissemination through interface roughening. <i>Science Advances</i>. AAAS. <a href="https://doi.org/10.1126/sciadv.aed0587">https://doi.org/10.1126/sciadv.aed0587</a> Z. Dunajova, S. Tasciyan, J. Majek, J. Merrin, R.P. Jenkins, E. Sahai, M.K. Sixt, E.B. Hannezo, Science Advances 12 (2026). Dunajova, Zuzana, et al. “Substrate Heterogeneity Promotes Cancer Cell Dissemination through Interface Roughening.” <i>Science Advances</i>, vol. 12, no. 37, eaed0587, AAAS, 2026, doi:<a href="https://doi.org/10.1126/sciadv.aed0587">10.1126/sciadv.aed0587</a>. 229632026-09-20T22:01:48Z2026-10-06T11:36:34Z