Unraveling the metastasis-preventing effect of miR-200c in vitro and in vivo.

Advanced breast cancer, as well as ineffective treatments leading to surviving cancer cells, can result in the dissemination of these malignant cells from the primary tumor to distant organs. Recent research has shown that microRNA 200c (miR-200c) can hamper certain steps of the invasion-metastasis cascade. However, it is still unclear whether miR-200c expression alone is sufficient to prevent breast cancer cells from metastasis formation.

Ion-mediated condensation controls the mechanics of mitotic chromosomes.

During mitosis in eukaryotic cells, mechanical forces generated by the mitotic spindle pull the sister chromatids into the nascent daughter cells. How do mitotic chromosomes achieve the necessary mechanical stiffness and stability to maintain their integrity under these forces? Here we use optical tweezers to show that ions involved in physiological chromosome condensation are crucial for chromosomal stability, stiffness and viscous dissipation. We combine these experiments with high-salt histone depletion and theory to show that chromosomal elasticity originates from the chromatin fibre behaving as a flexible polymer, whereas energy dissipation can be explained by modelling chromatin loops as an entangled polymer solution.

Loop-extruders alter bacterial chromosome topology to direct entropic forces for segregation.

Entropic forces have been argued to drive bacterial chromosome segregation during replication. In many bacterial species, however, specifically evolved mechanisms, such as loop-extruding SMC complexes and the ParABS origin segregation system, contribute to or are even required for chromosome segregation, suggesting that entropic forces alone may be insufficient. The interplay between and the relative contributions of these segregation mechanisms remain unclear.

Physical models of bacterial chromosomes.

The interplay between bacterial chromosome organization and functions such as transcription and replication can be studied in increasing detail using novel experimental techniques. Interpreting the resulting quantitative data, however, can be theoretically challenging. In this minireview, we discuss how connecting experimental observations to biophysical theory and modeling can give rise to new insights on bacterial chromosome organization.

Learning dynamical models of single and collective cell migration: a review.

Single and collective cell migration are fundamental processes critical for physiological phenomena ranging from embryonic development and immune response to wound healing and cancer metastasis. To understand cell migration from a physical perspective, a broad variety of models for the underlying physical mechanisms that govern cell motility have been developed. A key challenge in the development of such models is how to connect them to experimental observations, which often exhibit complex stochastic behaviours.

Geometry-Sensitive Protrusion Growth Directs Confined Cell Migration.

The migratory dynamics of cells can be influenced by the complex microenvironment through which they move. It remains unclear how the motility machinery of confined cells responds and adapts to their microenvironment. Here, we propose a biophysical mechanism for a geometry-dependent coupling between cellular protrusions and the nucleus that leads to directed migration.

Curvature induces active velocity waves in rotating spherical tissues.

The multicellular organization of diverse systems, including embryos, intestines, and tumors relies on coordinated cell migration in curved environments. In these settings, cells establish supracellular patterns of motion, including collective rotation and invasion. While such collective modes have been studied extensively in flat systems, the consequences of geometrical and topological constraints on collective migration in curved systems are largely unknown.

Nonlinear mechanics of human mitotic chromosomes.

In preparation for mitotic cell division, the nuclear DNA of human cells is compacted into individualized, X-shaped chromosomes. This metamorphosis is driven mainly by the combined action of condensins and topoisomerase IIα (TOP2A), and has been observed using microscopy for over a century. Nevertheless, very little is known about the structural organization of a mitotic chromosome.

Irreversibility in linear systems with colored noise.

Time irreversibility is a distinctive feature of nonequilibrium dynamics and several measures of irreversibility have been introduced to assess the distance from thermal equilibrium of a stochastically driven system. While the dynamical noise is often approximated as white, in many real applications the time correlations of the random forces can actually be significantly long-lived compared to the relaxation times of the driven system. We analyze the effects of temporal correlations in the noise on commonly used measures of irreversibility and demonstrate how the theoretical framework for white-noise-driven systems naturally generalizes to the case of colored noise.

Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration.

Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single-cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-cadherin junctions, central components of intercellular contacts, is still controversial.

Nonlinear stress relaxation of transiently crosslinked biopolymer networks.

A long-standing puzzle in the rheology of living cells is the origin of the experimentally observed long-time stress relaxation. The mechanics of the cell is largely dictated by the cytoskeleton, which is a biopolymer network consisting of transient crosslinkers, allowing for stress relaxation over time. Moreover, these networks are internally stressed due to the presence of molecular motors.

Theory of Active Intracellular Transport by DNA Relaying.

The spatiotemporal organization of bacterial cells is crucial for the active segregation of replicating chromosomes. In several species, including Caulobacter crescentus, the ATPase ParA binds to DNA and forms a gradient along the long cell axis. The ParB partition complex on the newly replicated chromosome translocates up this ParA gradient, thereby contributing to chromosome segregation.

Learning the distribution of single-cell chromosome conformations in bacteria reveals emergent order across genomic scales.

The order and variability of bacterial chromosome organization, contained within the distribution of chromosome conformations, are unclear. Here, we develop a fully data-driven maximum entropy approach to extract single-cell 3D chromosome conformations from Hi-C experiments on the model organism Caulobacter crescentus. The predictive power of our model is validated by independent experiments.

Learning the dynamics of cell-cell interactions in confined cell migration.

The migratory dynamics of cells in physiological processes, ranging from wound healing to cancer metastasis, rely on contact-mediated cell-cell interactions. These interactions play a key role in shaping the stochastic trajectories of migrating cells. While data-driven physical formalisms for the stochastic migration dynamics of single cells have been developed, such a framework for the behavioral dynamics of interacting cells still remains elusive.

Learning the non-equilibrium dynamics of Brownian movies.

Time-lapse microscopy imaging provides direct access to the dynamics of soft and living systems. At mesoscopic scales, such microscopy experiments reveal intrinsic thermal and non-equilibrium fluctuations. These fluctuations, together with measurement noise, pose a challenge for the dynamical analysis of these Brownian movies.

Inferring the Dynamics of Underdamped Stochastic Systems.

Many complex systems, ranging from migrating cells to animal groups, exhibit stochastic dynamics described by the underdamped Langevin equation. Inferring such an equation of motion from experimental data can provide profound insight into the physical laws governing the system. Here, we derive a principled framework to infer the dynamics of underdamped stochastic systems from realistic experimental trajectories, sampled at discrete times and subject to measurement errors.

Area and Geometry Dependence of Cell Migration in Asymmetric Two-State Micropatterns.

Microstructured surfaces provide a unique framework to probe cell migration and cytoskeletal dynamics in a standardized manner. Here, we report on the steady-state occupancy probability of cells in asymmetric two-state microstructures that consist of two fibronectin-coated adhesion sites connected by a thin guidance cue. In these dumbbell-like structures, cells transition between the two sites in a repeated and stochastic manner, and average dwell times in the respective microenvironments are determined from the cell trajectories.

A lattice kinetic Monte-Carlo method for simulating chromosomal dynamics and other (non-)equilibrium bio-assemblies.

Biological assemblies in living cells such as chromosomes constitute large many-body systems that operate in a fluctuating, out-of-equilibrium environment. Since a brute-force simulation of that many degrees of freedom is currently computationally unfeasible, it is necessary to perform coarse-grained stochastic simulations. Here, we develop all tools necessary to write a lattice kinetic Monte-Carlo (LKMC) algorithm capable of performing such simulations.