TY - JOUR AB - Metazoan development relies on the formation and remodeling of cell-cell contacts. Dynamic reorganization of adhesion receptors and the actomyosin cell cortex in space and time plays a central role in cell-cell contact formation and maturation. Nevertheless, how this process is mechanistically achieved when new contacts are formed remains unclear. Here, by building a biomimetic assay composed of progenitor cells adhering to supported lipid bilayers functionalized with E-cadherin ectodomains, we show that cortical F-actin flows, driven by the depletion of myosin-2 at the cell contact center, mediate the dynamic reorganization of adhesion receptors and cell cortex at the contact. E-cadherin-dependent downregulation of the small GTPase RhoA at the forming contact leads to both a depletion of myosin-2 and a decrease of F-actin at the contact center. At the contact rim, in contrast, myosin-2 becomes enriched by the retraction of bleb-like protrusions, resulting in a cortical tension gradient from the contact rim to its center. This tension gradient, in turn, triggers centrifugal F-actin flows, leading to further accumulation of F-actin at the contact rim and the progressive redistribution of E-cadherin from the contact center to the rim. Eventually, this combination of actomyosin downregulation and flows at the contact determines the characteristic molecular organization, with E-cadherin and F-actin accumulating at the contact rim, where they are needed to mechanically link the contractile cortices of the adhering cells. AU - Arslan, Feyza N AU - Hannezo, Edouard B AU - Merrin, Jack AU - Loose, Martin AU - Heisenberg, Carl-Philipp J ID - 14795 IS - 1 JF - Current Biology SN - 0960-9822 TI - Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts VL - 34 ER - TY - JOUR AB - Electrostatic correlations between ions dissolved in water are known to impact their transport properties in numerous ways, from conductivity to ion selectivity. The effects of these correlations on the solvent itself remain, however, much less clear. In particular, the addition of salt has been consistently reported to affect the solution’s viscosity, but most modeling attempts fail to reproduce experimental data even at moderate salt concentrations. Here, we use an approach based on stochastic density functional theory, which accurately captures charge fluctuations and correlations. We derive a simple analytical expression for the viscosity correction in concentrated electrolytes, by directly linking it to the liquid’s structure factor. Our prediction compares quantitatively to experimental data at all temperatures and all salt concentrations up to the saturation limit. This universal link between the microscopic structure and viscosity allows us to shed light on the nanoscale dynamics of water and ions under highly concentrated and correlated conditions. AU - Robin, Paul ID - 15024 IS - 6 JF - Journal of Chemical Physics SN - 0021-9606 TI - Correlation-induced viscous dissipation in concentrated electrolytes VL - 160 ER - TY - CHAP AB - The mammary gland consists of a bilayered epithelial structure with an extensively branched morphology. The majority of this epithelial tree is laid down during puberty, during which actively proliferating terminal end buds repeatedly elongate and bifurcate to form the basic structure of the ductal tree. Mammary ducts consist of a basal and luminal cell layer with a multitude of identified sub-lineages within both layers. The understanding of how these different cell lineages are cooperatively driving branching morphogenesis is a problem of crossing multiple scales, as this requires information on the macroscopic branched structure of the gland, as well as data on single-cell dynamics driving the morphogenic program. Here we describe a method to combine genetic lineage tracing with whole-gland branching analysis. Quantitative data on the global organ structure can be used to derive a model for mammary gland branching morphogenesis and provide a backbone on which the dynamics of individual cell lineages can be simulated and compared to lineage-tracing approaches. Eventually, these quantitative models and experiments allow to understand the couplings between the macroscopic shape of the mammary gland and the underlying single-cell dynamics driving branching morphogenesis. AU - Hannezo, Edouard B AU - Scheele, Colinda L.G.J. ED - Margadant, Coert ID - 12428 SN - 9781071628867 T2 - Cell Migration in Three Dimensions TI - A Guide Toward Multi-scale and Quantitative Branching Analysis in the Mammary Gland VL - 2608 ER - TY - JOUR AB - 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. AU - Brandstätter, Tom AU - Brückner, David AU - Han, Yu Long AU - Alert, Ricard AU - Guo, Ming AU - Broedersz, Chase P. ID - 12818 JF - Nature Communications TI - Curvature induces active velocity waves in rotating spherical tissues VL - 14 ER - TY - THES AB - Pattern formation is of great importance for its contribution across different biological behaviours. During developmental processes for example, patterns of chemical gradients are established to determine cell fate and complex tissue patterns emerge to define structures such as limbs and vascular networks. Patterns are also seen in collectively migrating groups, for instance traveling waves of density emerging in moving animal flocks as well as collectively migrating cells and tissues. To what extent these biological patterns arise spontaneously through the local interaction of individual constituents or are dictated by higher level instructions is still an open question however there is evidence for the involvement of both types of process. Where patterns arise spontaneously there is a long standing interest in how far the interplay of mechanics, e.g. force generation and deformation, and chemistry, e.g. gene regulation and signaling, contributes to the behaviour. This is because many systems are able to both chemically regulate mechanical force production and chemically sense mechanical deformation, forming mechano-chemical feedback loops which can potentially become unstable towards spatio and/or temporal patterning. We work with experimental collaborators to investigate the possibility that this type of interaction drives pattern formation in biological systems at different scales. We focus first on tissue-level ERK-density waves observed during the wound healing response across different systems where many previous studies have proposed that patterns depend on polarized cell migration and arise from a mechanical flocking-like mechanism. By combining theory with mechanical and optogenetic perturbation experiments on in vitro monolayers we instead find evidence for mechanochemical pattern formation involving only scalar bilateral feedbacks between ERK signaling and cell contraction. We perform further modeling and experiment to study how this instability couples with polar cell migration in order to produce a robust and efficient wound healing response. In a following chapter we implement ERK-density coupling and cell migration in a 2D active vertex model to investigate the interaction of ERK-density patterning with different tissue rheologies and find that the spatio-temporal dynamics are able to both locally and globally fluidize a tissue across the solid-fluid glass transition. In a last chapter we move towards lower spatial scales in the context of subcellular patterning of the cell cytoskeleton where we investigate the transition between phases of spatially homogeneous temporal oscillations and chaotic spatio-temporal patterning in the dynamics of myosin and ROCK activities (a motor component of the actomyosin cytoskeleton and its activator). Experimental evidence supports an intrinsic chemical oscillator which we encode in a reaction model and couple to a contractile active gel description of the cell cortex. The model exhibits phases of chemical oscillations and contractile spatial patterning which reproduce many features of the dynamics seen in Drosophila oocyte epithelia in vivo. However, additional pharmacological perturbations to inhibit myosin contractility leaves the role of contractile instability unclear. We discuss alternative hypotheses and investigate the possibility of reaction-diffusion instability. AU - Boocock, Daniel R ID - 12964 SN - 2663-337X TI - Mechanochemical pattern formation across biological scales ER - TY - JOUR AB - Living tissues are characterized by an intrinsically mechanochemical interplay of active physical forces and complex biochemical signaling pathways. Either feature alone can give rise to complex emergent phenomena, for example, mechanically driven glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion instabilities. An important question is how to quantitatively assess the contribution of these different cues to the large-scale dynamics of biological materials. We address this in Madin-Darby canine kidney (MDCK) monolayers, considering both mechanochemical feedback between extracellular signal-regulated kinase (ERK) signaling activity and cellular density as well as a mechanically active tissue rheology via a self-propelled vertex model. We show that the relative strength of active migration forces to mechanochemical couplings controls a transition from a uniform active glass to periodic spatiotemporal waves. We parametrize the model from published experimental data sets on MDCK monolayers and use it to make new predictions on the correlation functions of cellular dynamics and the dynamics of topological defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers are best described by an intermediary parameter region in which both mechanochemical couplings and noisy active propulsion have a strong influence on the dynamics. Finally, we study how tissue rheology and ERK waves produce feedback on one another and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical waves at both the local and global levels. AU - Boocock, Daniel R AU - Hirashima, Tsuyoshi AU - Hannezo, Edouard B ID - 14277 IS - 1 JF - PRX Life SN - 2835-8279 TI - Interplay between mechanochemical patterning and glassy dynamics in cellular monolayers VL - 1 ER - TY - JOUR AB - Surface curvature both emerges from, and influences the behavior of, living objects at length scales ranging from cell membranes to single cells to tissues and organs. The relevance of surface curvature in biology is supported by numerous experimental and theoretical investigations in recent years. In this review, first, a brief introduction to the key ideas of surface curvature in the context of biological systems is given and the challenges that arise when measuring surface curvature are discussed. Giving an overview of the emergence of curvature in biological systems, its significance at different length scales becomes apparent. On the other hand, summarizing current findings also shows that both single cells and entire cell sheets, tissues or organisms respond to curvature by modulating their shape and their migration behavior. Finally, the interplay between the distribution of morphogens or micro-organisms and the emergence of curvature across length scales is addressed with examples demonstrating these key mechanistic principles of morphogenesis. Overall, this review highlights that curved interfaces are not merely a passive by-product of the chemical, biological, and mechanical processes but that curvature acts also as a signal that co-determines these processes. AU - Schamberger, Barbara AU - Ziege, Ricardo AU - Anselme, Karine AU - Ben Amar, Martine AU - Bykowski, Michał AU - Castro, André P.G. AU - Cipitria, Amaia AU - Coles, Rhoslyn A. AU - Dimova, Rumiana AU - Eder, Michaela AU - Ehrig, Sebastian AU - Escudero, Luis M. AU - Evans, Myfanwy E. AU - Fernandes, Paulo R. AU - Fratzl, Peter AU - Geris, Liesbet AU - Gierlinger, Notburga AU - Hannezo, Edouard B AU - Iglič, Aleš AU - Kirkensgaard, Jacob J.K. AU - Kollmannsberger, Philip AU - Kowalewska, Łucja AU - Kurniawan, Nicholas A. AU - Papantoniou, Ioannis AU - Pieuchot, Laurent AU - Pires, Tiago H.V. AU - Renner, Lars D. AU - Sageman-Furnas, Andrew O. AU - Schröder-Turk, Gerd E. AU - Sengupta, Anupam AU - Sharma, Vikas R. AU - Tagua, Antonio AU - Tomba, Caterina AU - Trepat, Xavier AU - Waters, Sarah L. AU - Yeo, Edwina F. AU - Roschger, Andreas AU - Bidan, Cécile M. AU - Dunlop, John W.C. ID - 12710 IS - 13 JF - Advanced Materials SN - 0935-9648 TI - Curvature in biological systems: Its quantification, emergence, and implications across the scales VL - 35 ER - TY - GEN AB - The zip file includes source data used in the manuscript "CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration", as well as a representative Jupyter notebook to reproduce the main figures. Please see the preprint on bioRxiv and the DOI link there to access the final published version. Note the title change between the preprint and the published manuscript. A sample script for particle-based simulations of collective chemotaxis by self-generated gradients is also included (see Self-generated_chemotaxis_sample_script.ipynb) to generate exemplary cell trajectories. A detailed description of the simulation setup is provided in the supplementary information of the manuscipt. AU - Ucar, Mehmet C ID - 14279 TI - Source data for the manuscript "CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration" ER - TY - JOUR AB - As developing tissues grow in size and undergo morphogenetic changes, their material properties may be altered. Such changes result from tension dynamics at cell contacts or cellular jamming. Yet, in many cases, the cellular mechanisms controlling the physical state of growing tissues are unclear. We found that at early developmental stages, the epithelium in the developing mouse spinal cord maintains both high junctional tension and high fluidity. This is achieved via a mechanism in which interkinetic nuclear movements generate cell area dynamics that drive extensive cell rearrangements. Over time, the cell proliferation rate declines, effectively solidifying the tissue. Thus, unlike well-studied jamming transitions, the solidification uncovered here resembles a glass transition that depends on the dynamical stresses generated by proliferation and differentiation. Our finding that the fluidity of developing epithelia is linked to interkinetic nuclear movements and the dynamics of growth is likely to be relevant to multiple developing tissues. AU - Bocanegra, Laura AU - Singh, Amrita AU - Hannezo, Edouard B AU - Zagórski, Marcin P AU - Kicheva, Anna ID - 12837 JF - Nature Physics SN - 1745-2473 TI - Cell cycle dynamics control fluidity of the developing mouse neuroepithelium VL - 19 ER - TY - JOUR AB - To meet the physiological demands of the body, organs need to establish a functional tissue architecture and adequate size as the embryo develops to adulthood. In the liver, uni- and bipotent progenitor differentiation into hepatocytes and biliary epithelial cells (BECs), and their relative proportions, comprise the functional architecture. Yet, the contribution of individual liver progenitors at the organ level to both fates, and their specific proportion, is unresolved. Combining mathematical modelling with organ-wide, multispectral FRaeppli-NLS lineage tracing in zebrafish, we demonstrate that a precise BEC-to-hepatocyte ratio is established (i) fast, (ii) solely by heterogeneous lineage decisions from uni- and bipotent progenitors, and (iii) independent of subsequent cell type–specific proliferation. Extending lineage tracing to adulthood determined that embryonic cells undergo spatially heterogeneous three-dimensional growth associated with distinct environments. Strikingly, giant clusters comprising almost half a ventral lobe suggest lobe-specific dominant-like growth behaviours. We show substantial hepatocyte polyploidy in juveniles representing another hallmark of postembryonic liver growth. Our findings uncover heterogeneous progenitor contributions to tissue architecture-defining cell type proportions and postembryonic organ growth as key mechanisms forming the adult liver. AU - Unterweger, Iris A. AU - Klepstad, Julie AU - Hannezo, Edouard B AU - Lundegaard, Pia R. AU - Trusina, Ala AU - Ober, Elke A. ID - 14426 IS - 10 JF - PLoS Biology TI - Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics VL - 21 ER - TY - JOUR AB - 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. AU - Brückner, David AU - Chen, Hongtao AU - Barinov, Lev AU - Zoller, Benjamin AU - Gregor, Thomas ID - 13261 IS - 6652 JF - Science TI - Stochastic motion and transcriptional dynamics of pairs of distal DNA loci on a compacted chromosome VL - 380 ER - TY - JOUR AB - Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.e., tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms ensuring efficient tissue coverage remain poorly understood. Here, we use the mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing, genetic perturbations, whole-organ reconstructions and theoretical modeling to show that the dermal lymphatic capillaries tile space in an optimal, space-filling manner. This coverage is achieved by two complementary mechanisms: initial tissue invasion provides a non-optimal global scaffold via self-organized branching morphogenesis, while VEGF-C dependent side-branching from existing capillaries rapidly optimizes local coverage by directionally targeting low-density regions. With these two ingredients, we show that a minimal biophysical model can reproduce quantitatively whole-network reconstructions, across development and perturbations. Our results show that lymphatic capillary networks can exploit local self-organizing mechanisms to achieve tissue-scale optimization. AU - Ucar, Mehmet C AU - Hannezo, Edouard B AU - Tiilikainen, Emmi AU - Liaqat, Inam AU - Jakobsson, Emma AU - Nurmi, Harri AU - Vaahtomeri, Kari ID - 14378 JF - Nature Communications TI - Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks VL - 14 ER - TY - JOUR AB - Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization. AU - Alanko, Jonna H AU - Ucar, Mehmet C AU - Canigova, Nikola AU - Stopp, Julian A AU - Schwarz, Jan AU - Merrin, Jack AU - Hannezo, Edouard B AU - Sixt, Michael K ID - 14274 IS - 87 JF - Science Immunology KW - General Medicine KW - Immunology SN - 2470-9468 TI - CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration VL - 8 ER - TY - JOUR AB - Homeostatic balance in the intestinal epithelium relies on a fast cellular turnover, which is coordinated by an intricate interplay between biochemical signalling, mechanical forces and organ geometry. We review recent modelling approaches that have been developed to understand different facets of this remarkable homeostatic equilibrium. Existing models offer different, albeit complementary, perspectives on the problem. First, biomechanical models aim to explain the local and global mechanical stresses driving cell renewal as well as tissue shape maintenance. Second, compartmental models provide insights into the conditions necessary to keep a constant flow of cells with well-defined ratios of cell types, and how perturbations can lead to an unbalance of relative compartment sizes. A third family of models address, at the cellular level, the nature and regulation of stem fate choices that are necessary to fuel cellular turnover. We also review how these different approaches are starting to be integrated together across scales, to provide quantitative predictions and new conceptual frameworks to think about the dynamics of cell renewal in complex tissues. AU - Corominas-Murtra, Bernat AU - Hannezo, Edouard B ID - 12162 JF - Seminars in Cell & Developmental Biology KW - Cell Biology KW - Developmental Biology SN - 1084-9521 TI - Modelling the dynamics of mammalian gut homeostasis VL - 150-151 ER - TY - JOUR AB - 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. AU - Schwayer, Cornelia AU - Brückner, David ID - 14827 IS - 24 JF - Journal of Cell Science KW - Cell Biology SN - 0021-9533 TI - Connecting theory and experiment in cell and tissue mechanics VL - 136 ER - TY - JOUR AB - When in equilibrium, thermal forces agitate molecules, which then diffuse, collide and bind to form materials. However, the space of accessible structures in which micron-scale particles can be organized by thermal forces is limited, owing to the slow dynamics and metastable states. Active agents in a passive fluid generate forces and flows, forming a bath with active fluctuations. Two unanswered questions are whether those active agents can drive the assembly of passive components into unconventional states and which material properties they will exhibit. Here we show that passive, sticky beads immersed in a bath of swimming Escherichia coli bacteria aggregate into unconventional clusters and gels that are controlled by the activity of the bath. We observe a slow but persistent rotation of the aggregates that originates in the chirality of the E. coli flagella and directs aggregation into structures that are not accessible thermally. We elucidate the aggregation mechanism with a numerical model of spinning, sticky beads and reproduce quantitatively the experimental results. We show that internal activity controls the phase diagram and the structure of the aggregates. Overall, our results highlight the promising role of active baths in designing the structural and mechanical properties of materials with unconventional phases. AU - Grober, Daniel AU - Palaia, Ivan AU - Ucar, Mehmet C AU - Hannezo, Edouard B AU - Šarić, Anđela AU - Palacci, Jérémie A ID - 13971 JF - Nature Physics SN - 1745-2473 TI - Unconventional colloidal aggregation in chiral bacterial baths VL - 19 ER - TY - JOUR AB - 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. AU - Dunajova, Zuzana AU - Prats Mateu, Batirtze AU - Radler, Philipp AU - Lim, Keesiang AU - Brandis, Dörte AU - Velicky, Philipp AU - Danzl, Johann G AU - Wong, Richard W. AU - Elgeti, Jens AU - Hannezo, Edouard B AU - Loose, Martin ID - 13314 JF - Nature Physics SN - 1745-2473 TI - Chiral and nematic phases of flexible active filaments VL - 19 ER - TY - JOUR AB - Lymph nodes (LNs) comprise two main structural elements: fibroblastic reticular cells that form dedicated niches for immune cell interaction and capsular fibroblasts that build a shell around the organ. Immunological challenge causes LNs to increase more than tenfold in size within a few days. Here, we characterized the biomechanics of LN swelling on the cellular and organ scale. We identified lymphocyte trapping by influx and proliferation as drivers of an outward pressure force, causing fibroblastic reticular cells of the T-zone (TRCs) and their associated conduits to stretch. After an initial phase of relaxation, TRCs sensed the resulting strain through cell matrix adhesions, which coordinated local growth and remodeling of the stromal network. While the expanded TRC network readopted its typical configuration, a massive fibrotic reaction of the organ capsule set in and countered further organ expansion. Thus, different fibroblast populations mechanically control LN swelling in a multitier fashion. AU - Assen, Frank P AU - Abe, Jun AU - Hons, Miroslav AU - Hauschild, Robert AU - Shamipour, Shayan AU - Kaufmann, Walter AU - Costanzo, Tommaso AU - Krens, Gabriel AU - Brown, Markus AU - Ludewig, Burkhard AU - Hippenmeyer, Simon AU - Heisenberg, Carl-Philipp J AU - Weninger, Wolfgang AU - Hannezo, Edouard B AU - Luther, Sanjiv A. AU - Stein, Jens V. AU - Sixt, Michael K ID - 9794 JF - Nature Immunology SN - 1529-2908 TI - Multitier mechanics control stromal adaptations in swelling lymph nodes VL - 23 ER - TY - JOUR AB - 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. AU - Zisis, Themistoklis AU - Brückner, David AU - Brandstätter, Tom AU - Siow, Wei Xiong AU - d’Alessandro, Joseph AU - Vollmar, Angelika M. AU - Broedersz, Chase P. AU - Zahler, Stefan ID - 10530 IS - 1 JF - Biophysical Journal KW - Biophysics SN - 0006-3495 TI - Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration VL - 121 ER - TY - JOUR AB - Although rigidity and jamming transitions have been widely studied in physics and material science, their importance in a number of biological processes, including embryo development, tissue homeostasis, wound healing, and disease progression, has only begun to be recognized in the past few years. The hypothesis that biological systems can undergo rigidity/jamming transitions is attractive, as it would allow these systems to change their material properties rapidly and strongly. However, whether such transitions indeed occur in biological systems, how they are being regulated, and what their physiological relevance might be, is still being debated. Here, we review theoretical and experimental advances from the past few years, focusing on the regulation and role of potential tissue rigidity transitions in different biological processes. AU - Hannezo, Edouard B AU - Heisenberg, Carl-Philipp J ID - 10705 IS - 5 JF - Trends in Cell Biology SN - 0962-8924 TI - Rigidity transitions in development and disease VL - 32 ER -