Biology subjects

Brückner, D. B.

Publications and source records attributed to Brückner, D. B..

4 recordsLinked to original sources

bioRxiv2025

Cell heterogeneity and fate bistability drive tissue patterning during intestinal regeneration

Tissue regeneration relies on the ability of cells to undergo de novo patterning. While tissue patterning has been viewed as the transition from initially identical un-patterned cells to an arrangement of different cell types, recent evidence suggests that initial heterogeneities between cells modulate tissue-scale pattern formation. Yet, how such heterogeneities arise and, thereafter, regulate cell type emergence in a population of cells is poorly understood. Using in vivo and in vitro mouse regenerative systems, we identify a critical tissue density that is required to induce heterogeneous inactivation of the mechanosensor YAP1. Experimental and biophysical approaches demonstrate that YAP1 cell-to-cell heterogeneity pre-patterns the first cell fate decision, via both chromatin remodelling and a supracellular feedback between FOXA1 and Delta-Notch signalling. This feedback motif induces cell fate bistability endowing memory to the system and the maintenance of patterns during homeostasis. These findings reveal a generalisable framework in which transient cell-to-cell heterogeneity, regulated by tissue-scale properties, serves as a critical control parameter for the emergence of cell fate and stable patterning during regeneration.

cell biology↗

bioRxiv2024

Single cell migration along and against confined haptotactic gradients

Directed cell migration along gradients of extracellular matrix (ECM) density -a process called haptotaxis- plays a central role in morphogenesis, the immune response, and cancer invasion. It is commonly assumed that cells respond to these gradients by migrating directionally towards the regions of highest ligand density. In contrast with this view, here we show that cells exposed to micropatterned fibronectin gradients exhibit a complex repertoire of trajectories, including directed haptotactic migration up the gradient but also linear oscillations and circles with extended periods of migration down the gradient. To explain this behavior, we developed a biophysical model of haptotactic cell migration based on a coarse-grained molecular clutch model coupled to persistent stochastic polarity dynamics. While initial haptotactic migration is explained by the differential friction at the front and back of the cell, the observed complex trajectories over longer time scales arise from the interplay between differential friction, persistence, and physical confinement. Overall, our study reveals that confinement and persistence modulate the ability of cells to sense and respond to haptotactic cues and provides a framework to understand how cells navigate complex environments.

cell biology↗

bioRxiv2022

Geometry-driven migration efficiency of minimal cell clusters

The directed migration of epithelial cell collectives through coordinated movements plays a crucial role in various physiological and pathological processes and is increasingly understood at the level of large confluent monolayers. However, numerous processes rely on the migration of small groups of polarized epithelial clusters in complex environments, and their responses to external geometries remain poorly understood. To address this, we cultivated primary epithelial keratocyte tissues on adhesive microstripes, creating autonomous epithelial clusters with well-defined geometries. We showed that their migration efficiency is strongly influenced by the contact geometry, and the orientation of cell-cell contacts with respect to the direction of migration. To elucidate the underlying mechanisms, we systematically explored possible cell-cell interactions using a minimal active matter model. Our investigations revealed that a combination of velocity and polarity alignment with contact regulation of locomotion captures the experimental data, which we then validated via force and intracellular stress measurements. Furthermore, we predict that this combination of rules enables efficient navigation in complex geometries, which we confirm experimentally. Altogether, our findings provide a conceptual framework for extracting interaction rules governing the behavior of active systems interacting with physical boundaries, as well as designing principles for collective navigation in complex microenvironments.

biophysics↗

bioRxiv2021

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. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). 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 cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration.

biophysics↗