@article{14827,
  abstract     = {Understanding complex living systems, which are fundamentally constrained by physical phenomena, requires combining experimental data with theoretical physical and mathematical models. To develop such models, collaborations between experimental cell biologists and theoreticians are increasingly important but these two groups often face challenges achieving mutual understanding. To help navigate these challenges, this Perspective discusses different modelling approaches, including bottom-up hypothesis-driven and top-down data-driven models, and highlights their strengths and applications. Using cell mechanics as an example, we explore the integration of specific physical models with experimental data from the molecular, cellular and tissue level up to multiscale input. We also emphasize the importance of constraining model complexity and outline strategies for crosstalk between experimental design and model development. Furthermore, we highlight how physical models can provide conceptual insights and produce unifying and generalizable frameworks for biological phenomena. Overall, this Perspective aims to promote fruitful collaborations that advance our understanding of complex biological systems.},
  author       = {Schwayer, Cornelia and Brückner, David},
  issn         = {1477-9137},
  journal      = {Journal of Cell Science},
  keywords     = {Cell Biology},
  number       = {24},
  publisher    = {The Company of Biologists},
  title        = {{Connecting theory and experiment in cell and tissue mechanics}},
  doi          = {10.1242/jcs.261515},
  volume       = {136},
  year         = {2023},
}

@article{13261,
  abstract     = {Chromosomes in the eukaryotic nucleus are highly compacted. However, for many functional processes, including transcription initiation, the pairwise motion of distal chromosomal elements such as enhancers and promoters is essential and necessitates dynamic fluidity. Here, we used a live-imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output while systematically varying the genomic separation between these two DNA loci. Our analysis reveals the coexistence of a compact globular organization and fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation leading to long-ranged correlations. Thus, encounter times of DNA loci are much less dependent on genomic distance than predicted by existing polymer models, with potential consequences for eukaryotic gene expression.},
  author       = {Brückner, David and Chen, Hongtao and Barinov, Lev and Zoller, Benjamin and Gregor, Thomas},
  issn         = {1095-9203},
  journal      = {Science},
  number       = {6652},
  pages        = {1357--1362},
  publisher    = {American Association for the Advancement of Science},
  title        = {{Stochastic motion and transcriptional dynamics of pairs of distal DNA loci on a compacted chromosome}},
  doi          = {10.1126/science.adf5568},
  volume       = {380},
  year         = {2023},
}

@article{12818,
  abstract     = {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. Here, we discover a collective mode of cell migration in rotating spherical tissues manifesting as a propagating single-wavelength velocity wave. This wave is accompanied by an apparently incompressible supracellular flow pattern featuring topological defects as dictated by the spherical topology. Using a minimal active particle model, we reveal that this collective mode arises from the effect of curvature on the active flocking behavior of a cell layer confined to a spherical surface. Our results thus identify curvature-induced velocity waves as a mode of collective cell migration, impacting the dynamical organization of 3D curved tissues.},
  author       = {Brandstätter, Tom and Brückner, David and Han, Yu Long and Alert, Ricard and Guo, Ming and Broedersz, Chase P.},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Curvature induces active velocity waves in rotating spherical tissues}},
  doi          = {10.1038/s41467-023-37054-2},
  volume       = {14},
  year         = {2023},
}

@article{10530,
  abstract     = {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. Combining theoretical modeling with in vitro observations, we investigate the
collective spreading behavior of colonies of human cancer cells (T24). The spreading of these
colonies is driven by stochastic single-cell migration with frequent transient cell-cell contacts.
We find that inhibition of E- and N-Cadherin junctions decreases colony spreading and average
spreading velocities, without affecting the strength of correlations in spreading velocities of
neighboring cells. Based on a biophysical simulation model for cell migration, we show that the
behavioral changes upon disruption of these junctions can be explained by reduced repulsive
excluded volume interactions between cells. This suggests that in cancer cell migration,
cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than
cohesive interactions between cells, thereby promoting efficient cell spreading during collective
migration.
},
  author       = {Zisis, Themistoklis and Brückner, David and Brandstätter, Tom and Siow, Wei Xiong and d’Alessandro, Joseph and Vollmar, Angelika M. and Broedersz, Chase P. and Zahler, Stefan},
  issn         = {0006-3495},
  journal      = {Biophysical Journal},
  keywords     = {Biophysics},
  number       = {1},
  pages        = {P44--60},
  publisher    = {Elsevier},
  title        = {{Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration}},
  doi          = {10.1016/j.bpj.2021.12.006},
  volume       = {121},
  year         = {2022},
}

@article{12277,
  abstract     = {Cell migration in confining physiological environments relies on the concerted dynamics of several cellular components, including protrusions, adhesions with the environment, and the cell nucleus. However, it remains poorly understood how the dynamic interplay of these components and the cell polarity determine the emergent migration behavior at the cellular scale. Here, we combine data-driven inference with a mechanistic bottom-up approach to develop a model for protrusion and polarity dynamics in confined cell migration, revealing how the cellular dynamics adapt to confining geometries. Specifically, we use experimental data of joint protrusion-nucleus migration trajectories of cells on confining micropatterns to systematically determine a mechanistic model linking the stochastic dynamics of cell polarity, protrusions, and nucleus. This model indicates that the cellular dynamics adapt to confining constrictions through a switch in the polarity dynamics from a negative to a positive self-reinforcing feedback loop. Our model further reveals how this feedback loop leads to stereotypical cycles of protrusion-nucleus dynamics that drive the migration of the cell through constrictions. These cycles are disrupted upon perturbation of cytoskeletal components, indicating that the positive feedback is controlled by cellular migration mechanisms. Our data-driven theoretical approach therefore identifies polarity feedback adaptation as a key mechanism in confined cell migration.},
  author       = {Brückner, David and Schmitt, Matthew and Fink, Alexandra and Ladurner, Georg and Flommersfeld, Johannes and Arlt, Nicolas and Hannezo, Edouard B and Rädler, Joachim O. and Broedersz, Chase P.},
  issn         = {2160-3308},
  journal      = {Physical Review X},
  keywords     = {General Physics and Astronomy},
  number       = {3},
  publisher    = {American Physical Society},
  title        = {{Geometry adaptation of protrusion and polarity dynamics in confined cell migration}},
  doi          = {10.1103/physrevx.12.031041},
  volume       = {12},
  year         = {2022},
}