Biology subjects

Dunajova, Z.

Publications and source records attributed to Dunajova, Z..

2 recordsLinked to original sources

bioRxiv2025

Substrate heterogeneity promotes cancer cell dissemination

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.

biophysics↗

bioRxiv2022

Chiral and nematic phases of flexible active filaments

The emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, the tubulin-homolog FtsZ polymerizes into treadmilling filaments that further assemble into a cytoskeletal ring. Although minimal in vitro assays have shown the striking self-organization capacity of FtsZ filaments, such as dynamic chiral assemblies, how these large-scale structures emerge and relate to individual filament properties remains poorly understood. To understand this quantitatively, we combined minimal chiral active matter simulations with biochemical reconstitution experiments. Using STED and TIRF microscopy as well as high-speed AFM, we imaged the behavior of FtsZ filaments on different spatial scales. Simulations and experiments revealed that filament density and flexibility define the local and global order of the system: At intermediate densities, flexible filaments organize into chiral rings and polar bands, while an effectively nematic organization dominates for high filament densities and for mutant filaments with increased rigidity. Our predicted phase diagram captured these features quantitatively, demonstrating how filament flexibility, density and chirality cooperate with activity to give rise to a large repertoire of collective behaviors. These properties are likely important for the dynamic organization of soft chiral matter, including that of treadmilling FtsZ filaments during bacterial cell division.

biophysics↗