@article{19966, abstract = {Recently discovered nanofluidic memristors, have raised promises for the development of iontronics and neuromorphic computing with ions. Ionic memory effects are related to ion dynamics inside nanochannels, with timescales associated with the manifold physicochemical phenomena occurring at confined interfaces. Here, we explore experimentally the frequency-dependent current–voltage response of model nanochannels—namely glass nanopipettes—to investigate memory effects in ion transport. This characterisation, which we refer to as mem-spectrometry, highlights two characteristic frequencies, associated with short and long timescales of the order of 50 ms and 50 s in the present system. Whereas the former can be associated with ionic diffusion, very long timescales are difficult to explain with conventional transport phenomena. We develop a minimal model accounting for these mem-spectrometry results, pointing to surface charge regulation and ionic adsorption-desorption as possible origins for the long-term memory. Our work demonstrates the relevance of mem-spectrometry to highlight subtle ion transport properties in nanochannels, giving hereby new insights on the mechanisms governing ion transport and current rectification in charged conical nanopores.}, author = {Jouveshomme, Simon and Lizée, Mathieu and Robin, Paul and Bocquet, Lydéric}, issn = {1367-2630}, journal = {New Journal of Physics}, number = {6}, publisher = {IOP Publishing}, title = {{Multiple ionic memories in asymmetric nanochannels revealed by mem-spectrometry}}, doi = {10.1088/1367-2630/ade61b}, volume = {27}, year = {2025}, } @article{20056, abstract = {Theoretical studies have shown that stochasticity can affect the dynamics of ecosystems in counterintuitive ways. However, without knowing the equations governing the dynamics of populations or ecosystems, it is difficult to ascertain the role of stochasticity in real datasets. Therefore, the inverse problem of inferring the governing stochastic equations from datasets is important. Here, we present an equation discovery methodology that takes time series data of state variables as input and outputs a stochastic differential equation. We achieve this by combining traditional approaches from stochastic calculus with the equation discovery techniques. We demonstrate the generality of the method via several applications. First, we deliberately choose various stochastic models with fundamentally different governing equations, yet they produce nearly identical steady-state distributions. We show that we can recover the correct underlying equations, and thus infer the structure of their stability, accurately from the analysis of time series data alone. We demonstrate our method on two real-world datasets—fish schooling and single-cell migration—that have vastly different spatiotemporal scales and dynamics. We illustrate various limitations and potential pitfalls of the method and how to overcome them via diagnostic measures. Finally, we provide our open-source code via a package named PyDaDDy (Python Library for Data-Driven Dynamics).}, author = {Nabeel, Arshed and Karichannavar, Ashwin and Palathingal, Shuaib and Jhawar, Jitesh and Brückner, David and Raj M, Danny and Guttal, Vishwesha}, issn = {1537-5323}, journal = {The American Naturalist}, number = {4}, pages = {E100--E117}, publisher = {University of Chicago Press}, title = {{Discovering stochastic dynamical equations from ecological time series data}}, doi = {10.1086/734083}, volume = {205}, year = {2025}, } @article{20080, abstract = {Introduction: Acid-growth theory has been postulated in the 70s to explain the rapid elongation of plant cells in response to the hormone auxin. More recently, it has been demonstrated that activation of the proton ATPs pump (H+-ATPs) promoting acidification of the apoplast is the principal mechanism by which auxin and other hormones such as brassinosteroids (BR) induce cell elongation. Despite these advances, the impact of this acidification on the mechanical properties of the cell wall remained largely unexplored. Methods: Here, we use elongation assays of Arabidopsis thaliana hypocotyls and Atomic Force Microscopy (AFM) to correlate hormone-induced tissue elongation and local changes in cell wall mechanical properties. Furthermore, employing transgenic lines over-expressing Pectin Methyl Esterase (PME), along with calcium chelators, we investigate the effect of pectin modification in hormone-driven cell elongation. Results: We demonstrate that acidification of apoplast is necessary and sufficient to induce cell elongation through promoting cell wall softening. Moreover, we show that enhanced PME activity can induce both cell wall softening or stiffening in extracellular calcium dependent-manner and that tight control of PME activity is required for proper hypocotyl elongation. Discussion: Our results confirm a dual role of PME in plant cell elongation. However, further investigation is needed to assess the status of pectin following short- or long-term PME treatments in order to determine if pectin methyl-esterification might promote its degradation as well as the role of PME inhibitors upon PME induction.}, author = {Gallemi, Marçal and Montesinos López, Juan C and Zarevski, Nikola and Pribyl, Jan and Skládal, Petr and Hannezo, Edouard B and Benková, Eva}, issn = {1664-462X}, journal = {Frontiers in Plant Science}, publisher = {Frontiers Media}, title = {{Dual role of pectin methyl esterase activity in the regulation of plant cell wall biophysical properties}}, doi = {10.3389/fpls.2025.1612366}, volume = {16}, year = {2025}, } @article{20259, abstract = {Cell migration in narrow microenvironments occurs in numerous physiological processes. It involves successive cycles of confinement and release that drive important morphological changes. However, it remains unclear whether migrating cells can retain a memory of their past morphological states that could potentially facilitate their navigation through confined spaces. We demonstrate that local geometry governs a switch between two cell morphologies, thereby facilitating cell passage through long and narrow gaps. We combined cell migration assays on standardized microsystems with biophysical modelling and biochemical perturbations to show that migrating cells have a long-term memory of past confinement events. The morphological cell states correlate across transitions through actin cortex remodelling. These findings indicate that mechanical memory in migrating cells plays an active role in their migratory potential in confined environments.}, author = {Kalukula, Yohalie and Luciano, Marine and Simanov, Gleb and Charras, Guillaume and Brückner, David and Gabriele, Sylvain}, issn = {1745-2481}, journal = {Nature Physics}, pages = {1451--1461}, publisher = {Springer Nature}, title = {{The actin cortex acts as a mechanical memory of morphology in confined migrating cells}}, doi = {10.1038/s41567-025-02980-z}, volume = {21}, year = {2025}, } @article{20289, abstract = {Cell and tissue movement in development, cancer invasion, and immune response relies on chemical or mechanical guidance cues. In many systems, this behavior is locally directed by self-generated signaling gradients rather than long-range, prepatterned cues. However, how heterogeneous mixtures of cells interact nonreciprocally and navigate through self-generated gradients remains largely unexplored. Here, we introduce a theoretical framework for the self-organized chemotaxis of heterogeneous cell populations. We find that the relative chemotactic sensitivities of different cell populations control their long-time coupling and comigration dynamics, with boundary conditions such as external cell and attractant reservoirs substantially influencing the migration patterns. Our model predicts an optimal parameter regime that enables robust and colocalized migration. We test our theoretical predictions with in vitro experiments demonstrating the comigration of distinct immune cell populations, and quantitatively reproduce observed migration patterns under wild-type and perturbed conditions. Interestingly, immune cell comigration occurs close to the predicted optimal regime. Finally, we incorporate mechanical interactions into our framework, revealing a nontrivial interplay between chemotactic and mechanical nonreciprocity in driving collective migration. Together, our findings suggest that self-generated chemotaxis is a robust strategy for the navigation of mixed cell populations.}, author = {Ucar, Mehmet C and Zane, Alsberga and Alanko, Jonna H and Sixt, Michael K and Hannezo, Edouard B}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {34}, publisher = {National Academy of Sciences}, title = {{Self-generated chemotaxis of mixed cell populations}}, doi = {10.1073/pnas.2504064122}, volume = {122}, year = {2025}, } @phdthesis{20393, author = {Kishi, Kasumi}, issn = {2663-337X}, pages = {102}, publisher = {Institute of Science and Technology Austria}, title = {{Regulation of notochord and floor plate size during mouse development}}, doi = {10.15479/AT-ISTA-20393}, year = {2025}, } @article{20424, abstract = {Homeostasis relies on a precise balance of fate choices between renewal and differentiation. Although progress has been done to characterize the dynamics of single-cell fate choices, their underlying mechanistic basis often remains unclear. Concentrating on skin epidermis as a paradigm for multilayered tissues with complex fate choices, we develop a 3D vertex-based model with proliferation in the basal layer, showing that mechanical competition for space naturally gives rise to homeostasis and neutral drift dynamics that are seen experimentally. We then explore the effect of introducing mechanical heterogeneities between cellular subpopulations. We uncover that relatively small tension heterogeneities, reflected by distinct morphological changes in single-cell shapes, can be sufficient to heavily tilt cellular dynamics towards exponential growth. We thus derive a master relationship between cell shape and long-term clonal dynamics, which we validated during basal cell carcinoma initiation in mouse epidermis. Altogether, we propose a theoretical framework to link mechanical forces, quantitative cellular morphologies and cellular fate outcomes in complex tissues.}, author = {Sahu, Preeti and Monteiro-Ferreira, Sara and Canato, Sara and Soares, Raquel Maia and Sánchez-Danés, Adriana and Hannezo, Edouard B}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Mechanical control of cell fate decisions in the skin epidermis}}, doi = {10.1038/s41467-025-62882-9}, volume = {16}, year = {2025}, } @article{20431, abstract = {Haptotaxis is the process of directed cell migration along gradients of extracellular matrix density and is central to morphogenesis, immune responses 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 wide range of complex 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 behaviour, we developed a biophysical model of haptotactic cell migration based on a coarse-grained molecular clutch model coupled to persistent stochastic polarity dynamics. Although initial haptotactic migration is explained by the differential friction at the front and back of the cell, the observed complex trajectories over longer timescales 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 for understanding how cells navigate complex environments.}, author = {Fortunato, Isabela Corina and Brückner, David and Grosser, Steffen and Nautiyal, Rohit and Rossetti, Leone and Bosch-Padrós, Miquel and Trebicka, Jonel and Roca-Cusachs, Pere and Sunyer, Raimon and Hannezo, Edouard B and Trepat, Xavier}, issn = {1745-2481}, journal = {Nature Physics}, pages = {1638--1647}, publisher = {Springer Nature}, title = {{Single-cell migration along and against confined haptotactic gradients}}, doi = {10.1038/s41567-025-03015-3}, volume = {21}, year = {2025}, } @article{20670, abstract = {β-Barrel nanopores are involved in crucial biological processes, from ATP export in mitochondria to bacterial resistance, and represent a promising platform for emerging sequencing technologies. However, in contrast to ion channels, the understanding of the fundamental principles governing ion transport through these nanopores remains largely unexplored. Here we integrate experimental, numerical and theoretical approaches to elucidate ion transport mechanisms in β-barrel nanopores. We identify and characterize two distinct nonlinear phenomena: open-pore rectification and gating. Through extensive mutation analysis of aerolysin nanopores, we demonstrate that open-pore rectification is caused by ionic accumulation driven by the distribution of lumen charges. In addition, we provide converging evidence suggesting that gating is controlled by electric fields dissociating counterions from lumen charges, promoting local structural deformations. Our findings establish a rigorous framework for characterizing and understanding ion transport processes in protein-based nanopores, enabling the design of adaptable nanofluidic biotechnologies. We illustrate this by optimizing an aerolysin mutant for computing applications.}, author = {Mayer, Simon and Mitsioni, Marianna Fanouria and Robin, Paul and Van Den Heuvel, Lukas and Ronceray, Nathan and Marcaida, Maria Jose and Abriata, Luciano A. and Krapp, Lucien F. and Anton, Jana S. and Soussou, Sarah and Jeanneret-Grosjean, Justin and Fulciniti, Alessandro and Möller, Alexia and Vacle, Sarah and Feletti, Lely and Brinkerhoff, Henry and Laszlo, Andrew H. and Gundlach, Jens H. and Emmerich, Theo and Dal Peraro, Matteo and Radenovic, Aleksandra}, issn = {1748-3395}, journal = {Nature Nanotechnology}, publisher = {Springer Nature}, title = {{Lumen charge governs gated ion transport in β-barrel nanopores}}, doi = {10.1038/s41565-025-02052-6}, year = {2025}, } @article{20708, abstract = {In equilibrium, the physical properties of matter are set by the interactions between the constituents. In contrast, the energy input of the individual components controls the behavior of synthetic or living active matter. Great progress has been made in understanding the emergent phenomena in active fluids, though their inability to resist shear forces hinders their practical use. This motivates the exploration of active solids as shape-shifting materials, yet, we lack controlled synthetic systems to devise active solids with unconventional properties. Here we build active elastic beams from dozens of active colloids and unveil complex emergent behaviors such as self-oscillations or persistent rotations. Developing tensile tests at the microscale, we show that the active beams are ultrasoft materials, with large (nonequilibrium) fluctuations. Combining experiments, theory, and stochastic inference, we show that the dynamics of the active beams can be mapped on different phase transitions which are tuned by boundary conditions. More quantitatively, we assess all relevant parameters by independent measurements or first-principles calculations, and find that our theoretical description agrees with the experimental observations. Our results demonstrate that the simple addition of activity to an elastic beam unveils novel physics and can inspire design strategies for active solids and functional microscopic machines.}, author = {Martinet, Quentin and Li, Yuting I and Aubret, A. and Hannezo, Edouard B and Palacci, Jérémie A}, issn = {2160-3308}, journal = {Physical Review X}, number = {4}, publisher = {American Physical Society}, title = {{Emergent dynamics of active elastic microbeams}}, doi = {10.1103/rjk2-q2wh}, volume = {15}, year = {2025}, } @unpublished{21427, abstract = {While tumor malignancy has been extensively studied under the prism of genetic and epigenetic heterogeneity, tumor cell states also critically depend on reciprocal interactions with the microenvironment. This raises the hitherto untested possibility that heterogeneity of the untransformed tumor stroma can actively fuel malignant progression. As biological heterogeneity is inherently difficult to control, we adopted a reductionist approach and let tumor cells invade micro-engineered environments harboring obstacles with precision-controlled geometry. We find that not only the presence of obstacles, but more surprisingly their spatial disorder, causes a drastic shift from a collective to a single-cell mode of invasion – comparable in strength to cadherin loss. Combining live-imaging and perturbation experiments with minimal biophysical modeling, we demonstrate that cell detachments result both from local geometrical constraints and a global integration of spatial disorder over time. We show that different types of microenvironments map onto different universality classes of invasion dynamics - homogeneous substrates follow Kardar–Parisi–Zhang (KPZ) scaling, while disordered ones exhibit exponents consistent with KPZ with quenched disorder (KPZq). Our findings highlight generic physical principles for how the mode of cancer cell invasion depends on environmental heterogeneity, with potential implications to understand tumor evolution in vivo.}, author = {Dunajova, Zuzana and Tasciyan, Saren and Majek, Juraj and Merrin, Jack and Sahai, Erik and Sixt, Michael K and Hannezo, Edouard B}, booktitle = {bioRxiv}, title = {{Substrate heterogeneity promotes cancer cell dissemination through interface roughening}}, doi = {10.1101/2025.05.20.655037}, year = {2025}, } @phdthesis{20441, abstract = {Epithelial spreading plays a pivotal role in the development of organisms especially those such as zebrafish which require the epithelial enveloping layer (EVL) to spread to cover the substantial yolk surface during gastrulation. Epiboly requires the transition of the epithelium with cuboidal cells to form a thin, flat squamous epithelial sheet. During this transition, the cells show tissue-scale mechanosensation with mechanisms such as direct mechanical control over the axis of cell division. Cytoskeletal intermediate filaments play a crucial role in vertebrate cells, not only facilitating mechanical stability but also helping facilitate the mechanosensitive response of the cell. Mechanosenstivity displayed by intermediate filaments is due not just to their interesting physical properties but also to their interactions with other cytoskeletal elements such as actin and microtubules. Keratin is the predominant intermediate filament expressed in the EVL. It expresses concomitantly with the gastrulation movements of the developing embryo. Our work focuses on understanding the role and dynamics of the keratin cytoskeletal network in modulating the physical aspects of EVL spreading. We demonstrated with the combination of physical characterisation and manipulations of the EVL, utilising a variety of biophysical tools and microscopy, the mechanistic role of keratin in tissue spreading. Generating novel genetic morphants and mutants, we probe the effect that the loss of the keratin network has on the physiology of the epithelium and the developing embryo. We show that the changing organisation of the keratin network is important for changing EVL physical properties as the stress imposed on the EVL increases during epiboly. By modelling the epithelium, we study how the mechanical heterogeneity in an epithelium can feed back into a mechanical loop to the maturation of the keratin network and hence affect the mechanics of the epithelium. However, unlike what would be predicted by the effect of intermediate filaments in acting as a security belt and increasing the resistance of the epithelium, we observe that loss of keratin leads to a delay in the EVL movement. Using both local aspirations of the YSL and EVL ablations, we demonstrate the mechanistic facilitation of actin mechanosensation in a keratin-dependent manner. Furthermore, using chemical inhibitors of microtubule polymerisation, we provide insight into the mechanisms underlying the organisation and distribution of keratin. Interestingly, the phenotype observed upon this loss of microtubules shows that keratins interact with the nucleus through microtubular interactions. Together with these diverse observations, we describe the mechanosensory feedback between resilience and that is critical for uniform and robust spreading of the epithelium.}, author = {Naik, Suyash}, isbn = {978-3-99078-069-5}, issn = {2663-337X}, pages = {105}, publisher = {Institute of Science and Technology Austria}, title = {{Keratins act as global coordinators of tissue spreading through mechanosensitive feedback}}, doi = {10.15479/AT-ISTA-20441}, year = {2025}, } @unpublished{20465, abstract = {For tissues to spread, they must be deformable while maintaining their structural integrity. How these opposing requirements are balanced within spreading tissues is not yet well understood. Here, we show that keratin intermediate filaments function in epithelial spreading by adapting tissue mechanical resilience to the stresses arising in the tissue during the spreading process. By analysing the expansion of the enveloping cell layer (EVL) over the large yolk cell in early zebrafish embryos in vivo, we found that keratin network maturation in EVL cells is promoted by stresses building up within the spreading tissue. Through genetic interference and tissue rheology experiments, complemented by a vertex model with mechanochemical feedback, we demonstrate that stress-induced keratin network maturation in the EVL increases tissue viscosity, which is essential for preventing tissue rupture. Interestingly, keratins are also required in the yolk cell for mechanosensitive actomyosin network contraction and flow, the force-generating processes pulling the EVL. These dual mechanosensitive functions of keratins enable a balance between pulling force production in the yolk cell and the mechanical resilience of the EVL against stresses generated by these pulling forces, thereby ensuring uniform and robust tissue spreading.}, author = {Naik, Suyash and Keta, Yann-Edwin and Pranjic-Ferscha, Kornelija and Hannezo, Edouard B and Henkes, Silke and Heisenberg, Carl-Philipp J}, booktitle = {bioRxiv}, title = {{Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties}}, doi = {10.1101/2025.02.14.638262}, year = {2025}, } @article{18807, abstract = {Developing tissues interpret dynamic changes in morphogen activity to generate cell type diversity. To quantitatively study bone morphogenetic protein (BMP) signaling dynamics in the mouse neural tube, we developed an embryonic stem cell differentiation system tailored for growing tissues. Differentiating cells form striking self-organized patterns of dorsal neural tube cell types driven by sequential phases of BMP signaling that are observed both in vitro and in vivo. Data-driven biophysical modeling showed that these dynamics result from coupling fast negative feedback with slow positive regulation of signaling by the specification of an endogenous BMP source. Thus, in contrast to relays that propagate morphogen signaling in space, we identify a BMP signaling relay that operates in time. This mechanism allows for a rapid initial concentration-sensitive response that is robustly terminated, thereby regulating balanced sequential cell type generation. Our study provides an experimental and theoretical framework to understand how signaling dynamics are exploited in developing tissues.}, author = {Rus, Stefanie and Brückner, David and Minchington, Thomas and Greunz, Martina and Merrin, Jack and Hannezo, Edouard B and Kicheva, Anna}, issn = {1534-5807}, journal = {Developmental Cell}, number = {4}, pages = {567--580}, publisher = {Elsevier}, title = {{Self-organized pattern formation in the developing mouse neural tube by a temporal relay of BMP signaling}}, doi = {10.1016/j.devcel.2024.10.024}, volume = {60}, year = {2025}, } @article{14795, abstract = {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.}, author = {Arslan, Feyza N and Hannezo, Edouard B and Merrin, Jack and Loose, Martin and Heisenberg, Carl-Philipp J}, issn = {1879-0445}, journal = {Current Biology}, number = {1}, pages = {171--182.e8}, publisher = {Elsevier}, title = {{Adhesion-induced cortical flows pattern E-cadherin-mediated cell contacts}}, doi = {10.1016/j.cub.2023.11.067}, volume = {34}, year = {2024}, } @article{15024, abstract = {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.}, author = {Robin, Paul}, issn = {1089-7690}, journal = {Journal of Chemical Physics}, number = {6}, publisher = {AIP Publishing}, title = {{Correlation-induced viscous dissipation in concentrated electrolytes}}, doi = {10.1063/5.0188215}, volume = {160}, year = {2024}, } @article{15315, abstract = {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. In this review, we discuss recent advances in data-driven theoretical approaches that directly connect with experimental data to infer dynamical models of stochastic cell migration. Leveraging advances in nanofabrication, image analysis, and tracking technology, experimental studies now provide unprecedented large datasets on cellular dynamics. In parallel, theoretical efforts have been directed towards integrating such datasets into physical models from the single cell to the tissue scale with the aim of conceptualising the emergent behaviour of cells. We first review how this inference problem has been addressed in both freely migrating and confined cells. Next, we discuss why these dynamics typically take the form of underdamped stochastic equations of motion, and how such equations can be inferred from data. We then review applications of data-driven inference and machine learning approaches to heterogeneity in cell behaviour, subcellular degrees of freedom, and to the collective dynamics of multicellular systems. Across these applications, we emphasise how data-driven methods can be integrated with physical active matter models of migrating cells, and help reveal how underlying molecular mechanisms control cell behaviour. Together, these data-driven approaches are a promising avenue for building physical models of cell migration directly from experimental data, and for providing conceptual links between different length-scales of description.}, author = {Brückner, David and Broedersz, Chase P.}, issn = {1361-6633}, journal = {Reports on Progress in Physics}, number = {5}, publisher = {IOP Publishing}, title = {{Learning dynamical models of single and collective cell migration: a review}}, doi = {10.1088/1361-6633/ad36d2}, volume = {87}, year = {2024}, } @article{17104, abstract = {The homeostasis of epithelial tissue relies on a balance between the self-renewal of stem cell populations, cellular differentiation, and loss. Although this balance needs to be tightly regulated to avoid pathologies, such as tumor growth, the regulatory mechanisms, both cell-intrinsic and collective, which ensure tissue steady-state are still poorly understood. Here, we develop a computational model that incorporates basic assumptions of stem cell renewal into distinct populations and mechanical interactions between cells. We find that the model generates unexpected dynamic features: stem cells repel each other in the bulk tissue and are thus found rather isolated, as in a number of in vivo contexts. By mapping the system onto a gas of passive Brownian particles with effective repulsive interactions, that arise from the generated flows of differentiated cells, we show that we can quantitatively describe such stem cell distribution in tissues. The interaction potential between a pair of stem cells decays exponentially with a characteristic length that spans several cell sizes, corresponding to the volume of cells generated per stem cell division. Our findings may help understanding the dynamics of normal and cancerous epithelial tissues.}, author = {Krämer, Johannes C. and Hannezo, Edouard B and Gompper, Gerhard and Elgeti, Jens}, issn = {2542-4653}, journal = {SciPost Physics}, number = {4}, publisher = {SciPost Foundation}, title = {{Mechanically-driven stem cell separation in tissues caused by proliferating daughter cells}}, doi = {10.21468/scipostphys.16.4.097}, volume = {16}, year = {2024}, } @article{17123, abstract = {A key feature of many developmental systems is their ability to self-organize spatial patterns of functionally distinct cell fates. To ensure proper biological function, such patterns must be established reproducibly, by controlling and even harnessing intrinsic and extrinsic fluctuations. While the relevant molecular processes are increasingly well understood, we lack a principled framework to quantify the performance of such stochastic self-organizing systems. To that end, we introduce an information-theoretic measure for self-organized fate specification during embryonic development. We show that the proposed measure assesses the total information content of fate patterns and decomposes it into interpretable contributions corresponding to the positional and correlational information. By optimizing the proposed measure, our framework provides a normative theory for developmental circuits, which we demonstrate on lateral inhibition, cell type proportioning, and reaction–diffusion models of self-organization. This paves a way toward a classification of developmental systems based on a common information-theoretic language, thereby organizing the zoo of implicated chemical and mechanical signaling processes.}, author = {Brückner, David and Tkačik, Gašper}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {23}, publisher = {National Academy of Sciences}, title = {{Information content and optimization of self-organized developmental systems}}, doi = {10.1073/pnas.2322326121}, volume = {121}, year = {2024}, } @article{18446, abstract = {How living systems achieve precision in form and function despite their intrinsic stochasticity is a fundamental yet ongoing question in biology. We generated morphomaps of preimplantation embryogenesis in mouse, rabbit, and monkey embryos, and these morphomaps revealed that although blastomere divisions desynchronized passively, 8-cell embryos converged toward robust three-dimensional shapes. Using topological analysis and genetic perturbations, we found that embryos progressively changed their cellular connectivity to a preferred topology, which could be predicted by a physical model in which actomyosin contractility and noise facilitate topological transitions, lowering surface energy. This mechanism favored regular embryo packing and promoted a higher number of inner cells in the 16-cell embryo. Synchronized division reduced embryo packing and generated substantially more misallocated cells and fewer inner-cell–mass cells. These findings suggest that stochasticity in division timing contributes to robust patterning.}, author = {Fabrèges, Dimitri and Corominas-Murtra, Bernat and Moghe, Prachiti and Kickuth, Alison and Ichikawa, Takafumi and Iwatani, Chizuru and Tsukiyama, Tomoyuki and Daniel, Nathalie and Gering, Julie and Stokkermans, Anniek and Wolny, Adrian and Kreshuk, Anna and Duranthon, Véronique and Uhlman, Virginie and Hannezo, Edouard B and Hiiragi, Takashi}, issn = {1095-9203}, journal = {Science}, number = {6718}, publisher = {AAAS}, title = {{Temporal variability and cell mechanics control robustness in mammalian embryogenesis}}, doi = {10.1126/science.adh1145}, volume = {386}, year = {2024}, }