@article{14082, abstract = {Epithelial barrier function is commonly analyzed using transepithelial electrical resistance, which measures ion flux across a monolayer, or by adding traceable macromolecules and monitoring their passage across the monolayer. Although these methods measure changes in global barrier function, they lack the sensitivity needed to detect local or transient barrier breaches, and they do not reveal the location of barrier leaks. Therefore, we previously developed a method that we named the zinc-based ultrasensitive microscopic barrier assay (ZnUMBA), which overcomes these limitations, allowing for detection of local tight junction leaks with high spatiotemporal resolution. Here, we present expanded applications for ZnUMBA. ZnUMBA can be used in Xenopus embryos to measure the dynamics of barrier restoration and actin accumulation following laser injury. ZnUMBA can also be effectively utilized in developing zebrafish embryos as well as cultured monolayers of Madin–Darby canine kidney (MDCK) II epithelial cells. ZnUMBA is a powerful and flexible method that, with minimal optimization, can be applied to multiple systems to measure dynamic changes in barrier function with spatiotemporal precision.}, author = {Higashi, Tomohito and Stephenson, Rachel E. and Schwayer, Cornelia and Huljev, Karla and Higashi, Atsuko Y. and Heisenberg, Carl-Philipp J and Chiba, Hideki and Miller, Ann L.}, issn = {1477-9137}, journal = {Journal of Cell Science}, number = {15}, publisher = {The Company of Biologists}, title = {{ZnUMBA - a live imaging method to detect local barrier breaches}}, doi = {10.1242/jcs.260668}, volume = {136}, 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}, } @article{9999, abstract = {The developmental strategies used by progenitor cells to endure a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here we uncovered a progenitor cell allocation mechanism that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the surface epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-term apical contacts that enable the epithelial layer to pull a subset of progenitors along their way towards the vegetal pole. The remaining delaminated progenitors follow apically-attached progenitors’ movement by a co-attraction mechanism, avoiding sequestration by the adjacent endoderm, ensuring their fate and collective allocation at the differentiation site. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development. Impact Statement: Incomplete delamination serves as a cellular platform for coordinated tissue movements during development, guiding newly formed progenitor cell groups to the differentiation site.}, author = {Pulgar, Eduardo and Schwayer, Cornelia and Guerrero, Néstor and López, Loreto and Márquez, Susana and Härtel, Steffen and Soto, Rodrigo and Heisenberg, Carl Philipp and Concha, Miguel L.}, issn = {2050-084X}, journal = {eLife}, keywords = {cell delamination, apical constriction, dragging, mechanical forces, collective 18 locomotion, dorsal forerunner cells, zebrafish}, publisher = {eLife Sciences Publications}, title = {{Apical contacts stemming from incomplete delamination guide progenitor cell allocation through a dragging mechanism}}, doi = {10.7554/eLife.66483}, volume = {10}, year = {2021}, } @phdthesis{7186, abstract = {Tissue morphogenesis in developmental or physiological processes is regulated by molecular and mechanical signals. While the molecular signaling cascades are increasingly well described, the mechanical signals affecting tissue shape changes have only recently been studied in greater detail. To gain more insight into the mechanochemical and biophysical basis of an epithelial spreading process (epiboly) in early zebrafish development, we studied cell-cell junction formation and actomyosin network dynamics at the boundary between surface layer epithelial cells (EVL) and the yolk syncytial layer (YSL). During zebrafish epiboly, the cell mass sitting on top of the yolk cell spreads to engulf the yolk cell by the end of gastrulation. It has been previously shown that an actomyosin ring residing within the YSL pulls on the EVL tissue through a cable-constriction and a flow-friction motor, thereby dragging the tissue vegetal wards. Pulling forces are likely transmitted from the YSL actomyosin ring to EVL cells; however, the nature and formation of the junctional structure mediating this process has not been well described so far. Therefore, our main aim was to determine the nature, dynamics and potential function of the EVL-YSL junction during this epithelial tissue spreading. Specifically, we show that the EVL-YSL junction is a mechanosensitive structure, predominantly made of tight junction (TJ) proteins. The process of TJ mechanosensation depends on the retrograde flow of non-junctional, phase-separated Zonula Occludens-1 (ZO-1) protein clusters towards the EVL-YSL boundary. Interestingly, we could demonstrate that ZO-1 is present in a non-junctional pool on the surface of the yolk cell, and ZO-1 undergoes a phase separation process that likely renders the protein responsive to flows. These flows are directed towards the junction and mediate proper tension-dependent recruitment of ZO-1. Upon reaching the EVL-YSL junction ZO-1 gets incorporated into the junctional pool mediated through its direct actin-binding domain. When the non-junctional pool and/or ZO-1 direct actin binding is absent, TJs fail in their proper mechanosensitive responses resulting in slower tissue spreading. We could further demonstrate that depletion of ZO proteins within the YSL results in diminished actomyosin ring formation. This suggests that a mechanochemical feedback loop is at work during zebrafish epiboly: ZO proteins help in proper actomyosin ring formation and actomyosin contractility and flows positively influence ZO-1 junctional recruitment. Finally, such a mesoscale polarization process mediated through the flow of phase-separated protein clusters might have implications for other processes such as immunological synapse formation, C. elegans zygote polarization and wound healing.}, author = {Schwayer, Cornelia}, issn = {2663-337X}, pages = {107}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}}, doi = {10.15479/AT:ISTA:7186}, year = {2019}, } @article{7001, author = {Schwayer, Cornelia and Shamipour, Shayan and Pranjic-Ferscha, Kornelija and Schauer, Alexandra and Balda, M and Tada, M and Matter, K and Heisenberg, Carl-Philipp J}, issn = {1097-4172}, journal = {Cell}, number = {4}, pages = {937--952.e18}, publisher = {Cell Press}, title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}}, doi = {10.1016/j.cell.2019.10.006}, volume = {179}, year = {2019}, } @article{1096, author = {Schwayer, Cornelia and Sikora, Mateusz K and Slovakova, Jana and Kardos, Roland and Heisenberg, Carl-Philipp J}, journal = {Developmental Cell}, number = {6}, pages = {493 -- 506}, publisher = {Cell Press}, title = {{Actin rings of power}}, doi = {10.1016/j.devcel.2016.05.024}, volume = {37}, year = {2016}, }