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- ItemCurvature in Biological Systems: Its Quantification, Emergence, and Implications across the Scales(Weinheim : VCH Verl.-Ges., 2022) Schamberger, Barbara; Ziege, Ricardo; Anselme, Karine; Ben Amar, Martine; Bykowski, Michał; Castro, André P. G.; Cipitria, Amaia; Coles, Rhoslyn A.; Dimova, Rumiana; Eder, Michaela; Ehrig, Sebastian; Escudero, Luis M.; Evans, Myfanwy E.; Fernandes, Paulo R.; Fratzl, Peter; Geris, Liesbet; Gierlinger, Notburga; Hannezo, Edouard; Iglič, Aleš; Kirkensgaard, Jacob J. K.; Kollmannsberger, Philip; Kowalewska, Łucja; Kurniawan, Nicholas A.; Papantoniou, Ioannis; Pieuchot, Laurent; Pires, Tiago H. V.; Renner, Lars D.; Sageman‐Furnas, Andrew O.; Schröder‐Turk, Gerd E.; Sengupta, Anupam; Sharma, Vikas R.; Tagua, Antonio; Tomba, Caterina; Trepat, Xavier; Waters, Sarah L.; Yeo, Edwina F.; Roschger, Andreas; Bidan, Cécile M.; Dunlop, John W. C.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.
- ItemA novel, low-volume method for organ culture of embryonic kidneys that allows development of cortico-medullary anatomical organization(San Francisco, Calif. : Public Library of Science, 2010) Sebinger, D.D.R.; Unbekandt, M.; Ganeva, V.V.; Ofenbauer, A.; Werner, C.; Davies, J.A.Here, we present a novel method for culturing kidneys in low volumes of medium that offers more organotypic development compared to conventional methods. Organ culture is a powerful technique for studying renal development. It recapitulates many aspects of early development very well, but the established techniques have some disadvantages: in particular, they require relatively large volumes (1-3 mls) of culture medium, which can make high-throughput screens expensive, they require porous (filter) substrates which are difficult to modify chemically, and the organs produced do not achieve good cortico-medullary zonation. Here, we present a technique of growing kidney rudiments in very low volumes of medium-around 85 microliters-using silicone chambers. In this system, kidneys grow directly on glass, grow larger than in conventional culture and develop a clear anatomical cortico-medullary zonation with extended loops of Henle. © 2010 Sebinger et al.
- ItemPolyacrylamide Bead Sensors for in vivo Quantification of Cell-Scale Stress in Zebrafish Development([London] : Macmillan Publishers Limited, part of Springer Nature, 2019) Träber, N.; Uhlmann, K.; Girardo, S.; Kesavan, G.; Wagner, K.; Friedrichs, J.; Goswami, R.; Bai, K.; Brand, M.; Werner, C.; Balzani, D.; Guck, J.Mechanical stress exerted and experienced by cells during tissue morphogenesis and organ formation plays an important role in embryonic development. While techniques to quantify mechanical stresses in vitro are available, few methods exist for studying stresses in living organisms. Here, we describe and characterize cell-like polyacrylamide (PAAm) bead sensors with well-defined elastic properties and size for in vivo quantification of cell-scale stresses. The beads were injected into developing zebrafish embryos and their deformations were computationally analyzed to delineate spatio-temporal local acting stresses. With this computational analysis-based cell-scale stress sensing (COMPAX) we are able to detect pulsatile pressure propagation in the developing neural rod potentially originating from polarized midline cell divisions and continuous tissue flow. COMPAX is expected to provide novel spatio-temporal insight into developmental processes at the local tissue level and to facilitate quantitative investigation and a better understanding of morphogenetic processes. © 2019, The Author(s).
- ItemGlycosaminoglycan-based hydrogels to modulate heterocellular communication in in vitro angiogenesis models(London : Nature Publishing Group, 2014) Chwalek, K.; Tsurkan, M.V.; Freudenberg, U.; Werner, C.Angiogenesis, the outgrowth of blood vessels, is crucial in development, disease and regeneration. Studying angiogenesis in vitro remains challenging because the capillary morphogenesis of endothelial cells (ECs) is controlled by multiple exogenous signals. Therefore, a set of in situ-forming starPEG-heparin hydrogels was used to identify matrix parameters and cellular interactions that best support EC morphogenesis. We showed that a particular type of soft, matrix metalloproteinase-degradable hydrogel containing covalently bound integrin ligands and reversibly conjugated pro-angiogenic growth factors could boost the development of highly branched, interconnected, and lumenized endothelial capillary networks. Using these effective matrix conditions, 3D heterocellular interactions of ECs with different mural cells were demonstrated that enabled EC network modulation and maintenance of stable vascular capillaries over periods of about one month in vitro. The approach was also shown to permit in vitro tumor vascularization experiments with unprecedented levels of control over both ECs and tumor cells. In total, the introduced 3D hydrogel co-culture system could offer unique options for dissecting and adjusting biochemical, biophysical, and cell-cell triggers in tissue-related vascularization models.