@article{14378, abstract = {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.}, author = {Ucar, Mehmet C and Hannezo, Edouard B and Tiilikainen, Emmi and Liaqat, Inam and Jakobsson, Emma and Nurmi, Harri and Vaahtomeri, Kari}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks}}, doi = {10.1038/s41467-023-41456-7}, volume = {14}, year = {2023}, } @article{14426, abstract = {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.}, author = {Unterweger, Iris A. and Klepstad, Julie and Hannezo, Edouard B and Lundegaard, Pia R. and Trusina, Ala and Ober, Elke A.}, issn = {1545-7885}, journal = {PLoS Biology}, number = {10}, publisher = {Public Library of Science}, title = {{Lineage tracing identifies heterogeneous hepatoblast contribution to cell lineages and postembryonic organ growth dynamics}}, doi = {10.1371/journal.pbio.3002315}, volume = {21}, year = {2023}, } @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}, } @phdthesis{12964, abstract = {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.}, author = {Boocock, Daniel R}, isbn = {978-3-99078-032-9}, issn = {2663-337X}, pages = {146}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanochemical pattern formation across biological scales}}, doi = {10.15479/at:ista:12964}, year = {2023}, } @article{12837, abstract = {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.}, author = {Bocanegra, Laura and Singh, Amrita and Hannezo, Edouard B and Zagórski, Marcin P and Kicheva, Anna}, issn = {1745-2481}, journal = {Nature Physics}, pages = {1050--1058}, publisher = {Springer Nature}, title = {{Cell cycle dynamics control fluidity of the developing mouse neuroepithelium}}, doi = {10.1038/s41567-023-01977-w}, volume = {19}, year = {2023}, } @article{14274, abstract = {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.}, author = {Alanko, Jonna H and Ucar, Mehmet C and Canigova, Nikola and Stopp, Julian A and Schwarz, Jan and Merrin, Jack and Hannezo, Edouard B and Sixt, Michael K}, issn = {2470-9468}, journal = {Science Immunology}, keywords = {General Medicine, Immunology}, number = {87}, publisher = {American Association for the Advancement of Science}, title = {{CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration}}, doi = {10.1126/sciimmunol.adc9584}, volume = {8}, year = {2023}, } @misc{13116, abstract = {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 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 captures these features quantitatively, demonstrating how the flexibility, density and chirality of 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. }, author = {Dunajova, Zuzana and Prats Mateu, Batirtze and Radler, Philipp and Lim, Keesiang and Brandis, Dörte and Velicky, Philipp and Danzl, Johann G and Wong, Richard W. and Elgeti, Jens and Hannezo, Edouard B and Loose, Martin}, publisher = {Institute of Science and Technology Austria}, title = {{Chiral and nematic phases of flexible active filaments}}, doi = {10.15479/AT:ISTA:13116}, year = {2023}, } @article{13314, abstract = {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.}, author = {Dunajova, Zuzana and Prats Mateu, Batirtze and Radler, Philipp and Lim, Keesiang and Brandis, Dörte and Velicky, Philipp and Danzl, Johann G and Wong, Richard W. and Elgeti, Jens and Hannezo, Edouard B and Loose, Martin}, issn = {1745-2481}, journal = {Nature Physics}, pages = {1916--1926}, publisher = {Springer Nature}, title = {{Chiral and nematic phases of flexible active filaments}}, doi = {10.1038/s41567-023-02218-w}, volume = {19}, year = {2023}, } @article{10825, abstract = {In development, lineage segregation is coordinated in time and space. An important example is the mammalian inner cell mass, in which the primitive endoderm (PrE, founder of the yolk sac) physically segregates from the epiblast (EPI, founder of the fetus). While the molecular requirements have been well studied, the physical mechanisms determining spatial segregation between EPI and PrE remain elusive. Here, we investigate the mechanical basis of EPI and PrE sorting. We find that rather than the differences in static cell surface mechanical parameters as in classical sorting models, it is the differences in surface fluctuations that robustly ensure physical lineage sorting. These differential surface fluctuations systematically correlate with differential cellular fluidity, which we propose together constitute a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments and modeling, we identify cell surface dynamics as a key factor orchestrating the correct spatial segregation of the founder embryonic lineages.}, author = {Yanagida, Ayaka and Corujo-Simon, Elena and Revell, Christopher K. and Sahu, Preeti and Stirparo, Giuliano G. and Aspalter, Irene M. and Winkel, Alex K. and Peters, Ruby and De Belly, Henry and Cassani, Davide A.D. and Achouri, Sarra and Blumenfeld, Raphael and Franze, Kristian and Hannezo, Edouard B and Paluch, Ewa K. and Nichols, Jennifer and Chalut, Kevin J.}, issn = {1097-4172}, journal = {Cell}, number = {5}, pages = {777--793.e20}, publisher = {Cell Press}, title = {{Cell surface fluctuations regulate early embryonic lineage sorting}}, doi = {10.1016/j.cell.2022.01.022}, volume = {185}, year = {2022}, } @article{12209, abstract = {Embryo development requires biochemical signalling to generate patterns of cell fates and active mechanical forces to drive tissue shape changes. However, how these processes are coordinated, and how tissue patterning is preserved despite the cellular flows occurring during morphogenesis, remains poorly understood. Gastrulation is a crucial embryonic stage that involves both patterning and internalization of the mesendoderm germ layer tissue. Here we show that, in zebrafish embryos, a gradient in Nodal signalling orchestrates pattern-preserving internalization movements by triggering a motility-driven unjamming transition. In addition to its role as a morphogen determining embryo patterning, graded Nodal signalling mechanically subdivides the mesendoderm into a small fraction of highly protrusive leader cells, able to autonomously internalize via local unjamming, and less protrusive followers, which need to be pulled inwards by the leaders. The Nodal gradient further enforces a code of preferential adhesion coupling leaders to their immediate followers, resulting in a collective and ordered mode of internalization that preserves mesendoderm patterning. Integrating this dual mechanical role of Nodal signalling into minimal active particle simulations quantitatively predicts both physiological and experimentally perturbed internalization movements. This provides a quantitative framework for how a morphogen-encoded unjamming transition can bidirectionally couple tissue mechanics with patterning during complex three-dimensional morphogenesis.}, author = {Nunes Pinheiro, Diana C and Kardos, Roland and Hannezo, Edouard B and Heisenberg, Carl-Philipp J}, issn = {1745-2481}, journal = {Nature Physics}, keywords = {General Physics and Astronomy}, number = {12}, pages = {1482--1493}, publisher = {Springer Nature}, title = {{Morphogen gradient orchestrates pattern-preserving tissue morphogenesis via motility-driven unjamming}}, doi = {10.1038/s41567-022-01787-6}, volume = {18}, year = {2022}, } @article{12217, abstract = {The development dynamics and self-organization of glandular branched epithelia is of utmost importance for our understanding of diverse processes ranging from normal tissue growth to the growth of cancerous tissues. Using single primary murine pancreatic ductal adenocarcinoma (PDAC) cells embedded in a collagen matrix and adapted media supplementation, we generate organoids that self-organize into highly branched structures displaying a seamless lumen connecting terminal end buds, replicating in vivo PDAC architecture. We identify distinct morphogenesis phases, each characterized by a unique pattern of cell invasion, matrix deformation, protein expression, and respective molecular dependencies. We propose a minimal theoretical model of a branching and proliferating tissue, capturing the dynamics of the first phases. Observing the interaction of morphogenesis, mechanical environment and gene expression in vitro sets a benchmark for the understanding of self-organization processes governing complex organoid structure formation processes and branching morphogenesis.}, author = {Randriamanantsoa, S. and Papargyriou, A. and Maurer, H. C. and Peschke, K. and Schuster, M. and Zecchin, G. and Steiger, K. and Öllinger, R. and Saur, D. and Scheel, C. and Rad, R. and Hannezo, Edouard B and Reichert, M. and Bausch, A. R.}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids}}, doi = {10.1038/s41467-022-32806-y}, volume = {13}, year = {2022}, } @article{12253, abstract = {The sculpting of germ layers during gastrulation relies on the coordinated migration of progenitor cells, yet the cues controlling these long-range directed movements remain largely unknown. While directional migration often relies on a chemokine gradient generated from a localized source, we find that zebrafish ventrolateral mesoderm is guided by a self-generated gradient of the initially uniformly expressed and secreted protein Toddler/ELABELA/Apela. We show that the Apelin receptor, which is specifically expressed in mesodermal cells, has a dual role during gastrulation, acting as a scavenger receptor to generate a Toddler gradient, and as a chemokine receptor to sense this guidance cue. Thus, we uncover a single receptor–based self-generated gradient as the enigmatic guidance cue that can robustly steer the directional migration of mesoderm through the complex and continuously changing environment of the gastrulating embryo.}, author = {Stock, Jessica and Kazmar, Tomas and Schlumm, Friederike and Hannezo, Edouard B and Pauli, Andrea}, issn = {2375-2548}, journal = {Science Advances}, number = {37}, publisher = {American Association for the Advancement of Science}, title = {{A self-generated Toddler gradient guides mesodermal cell migration}}, doi = {10.1126/sciadv.add2488}, volume = {8}, year = {2022}, } @article{12274, abstract = {The morphology and functionality of the epithelial lining differ along the intestinal tract, but tissue renewal at all sites is driven by stem cells at the base of crypts1,2,3. Whether stem cell numbers and behaviour vary at different sites is unknown. Here we show using intravital microscopy that, despite similarities in the number and distribution of proliferative cells with an Lgr5 signature in mice, small intestinal crypts contain twice as many effective stem cells as large intestinal crypts. We find that, although passively displaced by a conveyor-belt-like upward movement, small intestinal cells positioned away from the crypt base can function as long-term effective stem cells owing to Wnt-dependent retrograde cellular movement. By contrast, the near absence of retrograde movement in the large intestine restricts cell repositioning, leading to a reduction in effective stem cell number. Moreover, after suppression of the retrograde movement in the small intestine, the number of effective stem cells is reduced, and the rate of monoclonal conversion of crypts is accelerated. Together, these results show that the number of effective stem cells is determined by active retrograde movement, revealing a new channel of stem cell regulation that can be experimentally and pharmacologically manipulated.}, author = {Azkanaz, Maria and Corominas-Murtra, Bernat and Ellenbroek, Saskia I. J. and Bruens, Lotte and Webb, Anna T. and Laskaris, Dimitrios and Oost, Koen C. and Lafirenze, Simona J. A. and Annusver, Karl and Messal, Hendrik A. and Iqbal, Sharif and Flanagan, Dustin J. and Huels, David J. and Rojas-Rodríguez, Felipe and Vizoso, Miguel and Kasper, Maria and Sansom, Owen J. and Snippert, Hugo J. and Liberali, Prisca and Simons, Benjamin D. and Katajisto, Pekka and Hannezo, Edouard B and van Rheenen, Jacco}, issn = {1476-4687}, journal = {Nature}, keywords = {Multidisciplinary}, number = {7919}, pages = {548--554}, publisher = {Springer Nature}, title = {{Retrograde movements determine effective stem cell numbers in the intestine}}, doi = {10.1038/s41586-022-04962-0}, volume = {607}, 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}, } @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{10705, abstract = {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.}, author = {Hannezo, Edouard B and Heisenberg, Carl-Philipp J}, issn = {1879-3088}, journal = {Trends in Cell Biology}, number = {5}, pages = {P433--444}, publisher = {Cell Press}, title = {{Rigidity transitions in development and disease}}, doi = {10.1016/j.tcb.2021.12.006}, volume = {32}, year = {2022}, } @article{9794, abstract = {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.}, author = {Assen, Frank P and Abe, Jun and Hons, Miroslav and Hauschild, Robert and Shamipour, Shayan and Kaufmann, Walter and Costanzo, Tommaso and Krens, Gabriel and Brown, Markus and Ludewig, Burkhard and Hippenmeyer, Simon and Heisenberg, Carl-Philipp J and Weninger, Wolfgang and Hannezo, Edouard B and Luther, Sanjiv A. and Stein, Jens V. and Sixt, Michael K}, issn = {1529-2916}, journal = {Nature Immunology}, pages = {1246--1255}, publisher = {Springer Nature}, title = {{Multitier mechanics control stromal adaptations in swelling lymph nodes}}, doi = {10.1038/s41590-022-01257-4}, volume = {23}, year = {2022}, } @misc{13058, abstract = {The zip file includes source data used in the main text of the manuscript "Theory of branching morphogenesis by local interactions and global guidance", as well as a representative Jupyter notebook to reproduce the main figures. A sample script for the simulations of branching and annihilating random walks is also included (Sample_script_for_simulations_of_BARWs.ipynb) to generate exemplary branched networks under external guidance. A detailed description of the simulation setup is provided in the supplementary information of the manuscipt.}, author = {Ucar, Mehmet C}, publisher = {Zenodo}, title = {{Source data for the manuscript "Theory of branching morphogenesis by local interactions and global guidance"}}, doi = {10.5281/ZENODO.5257160}, year = {2021}, } @misc{13068, abstract = {Source data and source code for the graphs in "Spatiotemporal dynamics of self-organized branching pancreatic cancer-derived organoids".}, author = {Randriamanantsoa, Samuel and Papargyriou, Aristeidis and Maurer, Carlo and Peschke, Katja and Schuster, Maximilian and Zecchin, Giulia and Steiger, Katja and Öllinger, Rupert and Saur, Dieter and Scheel, Christina and Rad, Roland and Hannezo, Edouard B and Reichert, Maximilian and Bausch, Andreas R.}, publisher = {Zenodo}, title = {{Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids}}, doi = {10.5281/ZENODO.5148117}, year = {2021}, } @article{10178, abstract = {In dense biological tissues, cell types performing different roles remain segregated by maintaining sharp interfaces. To better understand the mechanisms for such sharp compartmentalization, we study the effect of an imposed heterotypic tension at the interface between two distinct cell types in a fully 3D Voronoi model for confluent tissues. We find that cells rapidly sort and self-organize to generate a tissue-scale interface between cell types, and cells adjacent to this interface exhibit signature geometric features including nematic-like ordering, bimodal facet areas, and registration, or alignment, of cell centers on either side of the two-tissue interface. The magnitude of these features scales directly with the magnitude of the imposed tension, suggesting that biologists can estimate the magnitude of tissue surface tension between two tissue types simply by segmenting a 3D tissue. To uncover the underlying physical mechanisms driving these geometric features, we develop two minimal, ordered models using two different underlying lattices that identify an energetic competition between bulk cell shapes and tissue interface area. When the interface area dominates, changes to neighbor topology are costly and occur less frequently, which generates the observed geometric features.}, author = {Sahu, Preeti and Schwarz, J. M. and Manning, M. Lisa}, issn = {1367-2630}, journal = {New Journal of Physics}, number = {9}, publisher = {IOP Publishing}, title = {{Geometric signatures of tissue surface tension in a three-dimensional model of confluent tissue}}, doi = {10.1088/1367-2630/ac23f1}, volume = {23}, year = {2021}, }