@article{22963, abstract = {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.}, author = {Dunajova, Zuzana and Tasciyan, Saren and Majek, Juraj and Merrin, Jack and Jenkins, Robert P. and Sahai, Erik and Sixt, Michael K and Hannezo, Edouard B}, issn = {2375-2548}, journal = {Science Advances}, number = {37}, publisher = {AAAS}, title = {{Substrate heterogeneity promotes cancer cell dissemination through interface roughening}}, doi = {10.1126/sciadv.aed0587}, volume = {12}, year = {2026}, } @phdthesis{21423, abstract = {Biological systems, such as cytoskeletal filaments and multicellular collectives, exhibit rich self-organization driven by their intrinsic activity and physical constraints. Across scales, geometry plays a central role: the shape of active units and the structure of their environment strongly influence how order emerges in these far-from-equilibrium systems. In this thesis, we combine minimal active-matter models with bottom-up in vitro experiments to identify the principles by which geometry and activity shape collective behavior in biological matter. At the subcellular scale, we investigate how the physical properties of chiral FtsZ filaments govern their large-scale organization. Using a mesoscopic model validated by reconstituted filament assays, we show that filament shape, intrinsic curvature, and flexibility, together with activity-driven straightening, determine whether filaments form chiral rings, polar bands, or nematic-like states. Our model shows that small changes in filament mechanics produce large shifts in collective structures, revealing how the geometry of individual filaments amplifies through activity to control patterns relevant for bacterial cytokinesis. At the cellular scale, we examine how geometry of the external environment influences collective cancer cell migration. Experiments in controlled microfabricated obstacle environments demonstrate that geometric disorder alone can induce a transition from collective to single-cell invasion. A minimal model of active particles in disordered geometries reproduces these effects, demonstrating that cell dissemination results both from local geometrical constraints and a global integration of spatial disorder over time. Surprisingly, this transition is accompanied by a change in the universality class of interface dynamics, revealing that cell-environment interactions can shift the collective behavior of an invasive front purely through mechanics. In the last system, we study how cell-intrinsic geometry and chirality affect collective motion in confined and unconfined settings. Using a minimal model inspired by in vitro experiments, we analyze motile cells that exhibit persistent rotation due to intrinsic left-right asymmetry. In circular confinement, this simplified chiral model reproduces several experimentally observed features within specific parameter regimes. At high densities in unconfined environments, however, intrinsic chirality becomes masked even before the onset of the jamming transition. These results show that single-cell geometric asymmetry does not necessarily translate into large-scale chiral flows, offering new insight into how forces and symmetries shape collective motion in dense cellular systems. Overall, this work uncovers how geometric constraints – embedded in the intrinsic architecture of an active filament or encoded in the complexity of a microenvironment couple to active forces to generate different classes of complex behaviors. }, author = {Dunajova, Zuzana}, isbn = {978-3-99078-076-3}, issn = {2663-337X}, pages = {110}, publisher = {Institute of Science and Technology Austria}, title = {{Geometry-driven self-organization of migrating cells and chiral filaments}}, doi = {10.15479/AT-ISTA-21423}, year = {2026}, } @misc{21439, abstract = {These files contain supplementary movies accompanying the PhD thesis “Geometry-driven self-organization of migrating cells and chiral filaments” by Zuzana Dunajova (2026). The videos provide additional visual material supporting the experiments and results described in the thesis.}, author = {Dunajova, Zuzana}, publisher = {Institute of Science and Technology Austria}, title = {{Supplementary movies to PhD thesis “Geometry-driven self-organization of migrating cells and chiral filaments”}}, doi = {10.15479/AT-ISTA-21439}, year = {2026}, } @unpublished{21427, abstract = {While tumor malignancy has been extensively studied under the prism of genetic and epigenetic heterogeneity, tumor cell states also critically depend on reciprocal interactions with the microenvironment. This raises the hitherto untested possibility that heterogeneity of the untransformed tumor stroma can actively fuel malignant progression. As biological heterogeneity is inherently difficult to control, we adopted a reductionist approach and let tumor cells invade micro-engineered environments harboring obstacles with precision-controlled geometry. We find that not only the presence of obstacles, but more surprisingly their spatial disorder, causes a drastic shift from a collective to a single-cell mode of invasion – comparable in strength to cadherin loss. Combining live-imaging and perturbation experiments with minimal biophysical modeling, we demonstrate that cell detachments result both from local geometrical constraints and a global integration of spatial disorder over time. We show that different types of microenvironments map onto different universality classes of invasion dynamics - homogeneous substrates follow Kardar–Parisi–Zhang (KPZ) scaling, while disordered ones exhibit exponents consistent with KPZ with quenched disorder (KPZq). Our findings highlight generic physical principles for how the mode of cancer cell invasion depends on environmental heterogeneity, with potential implications to understand tumor evolution in vivo.}, author = {Dunajova, Zuzana and Tasciyan, Saren and Majek, Juraj and Merrin, Jack and Sahai, Erik and Sixt, Michael K and Hannezo, Edouard B}, booktitle = {bioRxiv}, title = {{Substrate heterogeneity promotes cancer cell dissemination through interface roughening}}, doi = {10.1101/2025.05.20.655037}, year = {2025}, } @misc{13116, abstract = {The emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, FtsZ -- a prokaryotic homologue of the eukaryotic protein tubulin -- polymerizes into treadmilling filaments that further organize into a cytoskeletal ring. In vitro, FtsZ filaments can form dynamic chiral assemblies. However, how the active and passive properties of individual filaments relate to these large-scale self-organized structures remains poorly understood. Here, we connect single filament properties with the mesoscopic scale by combining minimal active matter simulations and biochemical reconstitution experiments. We show that density and flexibility of active chiral filaments define their global order. At intermediate densities, curved, flexible filaments organize into chiral rings and polar bands. An effectively nematic organization dominates for high densities and for straight, mutant filaments with increased rigidity. Our predicted phase diagram captures these features quantitatively, demonstrating how the flexibility, density and chirality of active filaments affect their collective behaviour. Our findings shed light on the fundamental properties of active chiral matter and explain how treadmilling FtsZ filaments organize during bacterial cell division. }, author = {Dunajova, Zuzana and Prats Mateu, Batirtze and Radler, Philipp and Lim, Keesiang and Brandis, Dörte and Velicky, Philipp and Danzl, Johann G and Wong, Richard W. and Elgeti, Jens and Hannezo, Edouard B and Loose, Martin}, publisher = {Institute of Science and Technology Austria}, title = {{Chiral and nematic phases of flexible active filaments}}, doi = {10.15479/AT:ISTA:13116}, year = {2023}, } @article{13314, abstract = {The emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, FtsZ—a prokaryotic homologue of the eukaryotic protein tubulin—polymerizes into treadmilling filaments that further organize into a cytoskeletal ring. In vitro, FtsZ filaments can form dynamic chiral assemblies. However, how the active and passive properties of individual filaments relate to these large-scale self-organized structures remains poorly understood. Here we connect single-filament properties with the mesoscopic scale by combining minimal active matter simulations and biochemical reconstitution experiments. We show that the density and flexibility of active chiral filaments define their global order. At intermediate densities, curved, flexible filaments organize into chiral rings and polar bands. An effectively nematic organization dominates for high densities and for straight, mutant filaments with increased rigidity. Our predicted phase diagram quantitatively captures these features, demonstrating how the flexibility, density and chirality of the active filaments affect their collective behaviour. Our findings shed light on the fundamental properties of active chiral matter and explain how treadmilling FtsZ filaments organize during bacterial cell division.}, author = {Dunajova, Zuzana and Prats Mateu, Batirtze and Radler, Philipp and Lim, Keesiang and Brandis, Dörte and Velicky, Philipp and Danzl, Johann G and Wong, Richard W. and Elgeti, Jens and Hannezo, Edouard B and Loose, Martin}, issn = {1745-2481}, journal = {Nature Physics}, pages = {1916--1926}, publisher = {Springer Nature}, title = {{Chiral and nematic phases of flexible active filaments}}, doi = {10.1038/s41567-023-02218-w}, volume = {19}, year = {2023}, }