Speakers 2024

Andreas Bausch
Technische Universität München, Germany

Living matter relies on the self organization of its components into higher order structures, on the molecular as well as on the cellular, organ or even organism scale. Collective motion due to active transport processes has been shown to be a promising route for attributing fascinating order formation processes on these different length scales. Here I will present recent results on structure formation in organoid systems, demonstrating how mechanical feedback between extracellular matrix, proliferation and cell migration drives structure formation process in these multicellular model systems. I will present results on the developmental phase of mammary gland and pancreatic ducal adenocarcinoma organoids.

Hagan Bayley
University of Oxford, UK

By 3D printing, we have assembled synthetic tissues comprising patterned networks of thousands of aqueous droplets joined by lipid bilayers. A related printing technology has been used to pattern a variety of living cells, providing structures that include small tumours and fragments of neural tissue. The mm-scale printed structures can be used as building blocks for cm-scale structures ranging from synthetic axons to hybrid constructs containing both synthetic and living cells. An important goal is to be able to communicate with these constructs through external stimuli, have them process the incoming signals and accordingly produce outputs that are useful, for example, in medicine. Progress on these aspects of signaling will be described in my talk.   

Michael Boutros
Heidelberg University, Germany

Ada Cavalcanti-Adam
University of Bayreuth, Germany

Cancer progression is a complex process involving a series of intricate cellular interactions and migrations. Tumor cell spheroids, three-dimensional aggregates of cancer cells, closely mimic the in vivo microenvironment and offer invaluable insights into the mechanisms of cancer invasion. In this talk, I will elucidate how different materials can steer the invasion patterns and the solid-to-fluid transitions of cancer cells. By utilizing state-of-the-art bioengineering techniques, we have created innovative in vitro models that accurately emulate the tumor microenvironment’s physical and biochemical cues.

Our findings demonstrate that specific material properties, such as stiffness, topography, and chemical composition, significantly impact the migratory behavior of cancer cell spheroids. Through advanced live-cell imaging and traction force microscopy, we decipher the intricate interplay between cancer cells and the surrounding material. By employing biofunctionalized materials and targeted drugs, we influence cancer cell behavior, potentially halting their invasive patterns and interfering with their collective responses to the microenvironment.

Christopher Chen
Boston University, USA

Laura De Laporte
RWTH Aachen University, Germany

We apply polymeric molecular and nano- to micron-scale building blocks to assemble into soft 3D biomaterials with anisotropic and dynamic properties. Microgels and fibers are produced by technologies based on fiber spinning, microfluidics, and in-mold polymerization. To arrange the building blocks in a spatially controlled manner, self-assembly mechanisms and alignment by external magnetic fields are employed. Reactive rod-shaped microgels interlink and form macroporous constructs supporting 3D cell growth or cells are able to use microgels as bricks to build their own house. On the other hand, the Anisogel technology offers a solution to regenerate sensitive tissues with an oriented architecture, which requires a low invasive therapy. It can be injected as a liquid and structured in situ in a controlled manner with defined biochemical, mechanical, and structural parameters. Magnetoceptive, anisometric microgels or short fibers are incorporated to create a unidirectional structure. Cells and nerves grow in a linear manner and the fibronectin produced by fibroblasts is aligned. Regenerated nerves are functional with spontaneous activity and electrical signals propagating along the anisotropy axis of the material. Another developed platform is a thermoresponsive hydrogel system, encapsulated with plasmonic gold-nanorods, which actuates by oscillating light. This system elucidates how rapid hydrogel beating affects cell migration, focal adhesions, native production of extracellular matrix, and nuclear translocation of mechanosensitive proteins, depending on the amplitude and frequency of actuation. The time spent in the in vitro gym seems to affect myoblast differentiation and fibrosis, while actuation seems to induce mesenchymal stem cell differentiation into bone cells.

Jacopo di Russo
RWTH Aachen University, Germany

Mechanical properties regulate tissue functions at a multicellular length scale or mesoscale. These properties depend on the interaction of cells with their interfaces, hence on the balance between intercellular tension and the extracellular matrix (ECM) adhesion forces.

My group aims to dissect the role of cell-ECM and cell-cell communication in epithelial mechanobiology, starting from the medically relevant retinal epithelium. In contrast to the experimental investigation of traditional biological sciences, my laboratory uses cross-disciplinary approaches combining synthetic hydrogels with stem cell-based models. We particularly develop and adapt biohybrid systems where cells interact with hydrogels that are designed to control cell-cell or cell-ECM adhesion. Synthetic material allows the unique reduction of the degree of freedom in the cellular/tissue system, thus helping us to reveal phenotypical tissue plasticity and molecular function.

My talk will first give an overview of published work[1],[2] on understanding how ECM physical (elasticity) and biochemical cues (receptor density) impact epithelial system properties, namely stress heterogeneity and intercellular force coordination. I will show that these properties are not only in vitro observations but play pivotal roles in controlling our vision. A density gradient of ECM characterises the contractility of the retinal epithelium in vivo and modulates its efficiency in supporting photoreceptor cells’ homeostasis. Furthermore, I will show data from the ongoing work which addresses different aspects of the mechanobiology of tissue ageing. We optimised a phototunable hydrogel as substrates for epithelia to model ECM local remodelling on demand. Moreover, we developed microgels used as phototunable phantom cells to simulate age-related tissue mechanical anisotropy. Altogether, we can dissect the relationship between tissue mechanics and function by controlling the temporal and spatial properties of cellular interfaces.

[1]https://doi.org/10.7554/eLife.69861

[2] https://doi.org/10.1101/2023.02.24.529913

Daniela Duarte Campos
Heidelberg University, Germany

Bioprinting is an exciting technology that holds promise to fabricate tissues and organs both in vitro and in vivo. Besides engineering lab-grown in vitro models, current advances are focussed in bringing bioprinting technologies from the bench to the operating room. Scientists around the world are continuously improving the complexity and precision of bioprinting methods, which still in this decade will not only allow us to engineer new tissues and even organs, but also to change the way transplantation medicine is done. As with many new fields, this technology comes with challenges, such as controlling cell survival and function for being exposed to shear stress during bioprinting. This is one major hurdle that needs to be addressed by scientists in order to allow this young research field to achieve its first significant impact in medicine. In this talk, I will show bioinspired strategies and robotics that our lab is developing to minimize or flank the effect of shear stress for the purpose of building tissue using cells and cell aggregates.

Peer Fischer
Heidelberg University, Germany

Edouard Hannezo
Institute of Science and Technology, Austria

How pattern and form are generated in a reproducible manner during embryogenesis remains poorly understood. Intestinal organoid morphogenesis involves a number of mechanochemical regulators, including cell-type specific cytoskeletal forces and osmotically-driven lumen volume changes. However, whether and how these forces are coordinated in time and space, via feedbacks, to ensure robust morphogenesis remains unclear. Here, we propose a minimal physical model of organoid morphogenesis with local cellular mechano-sensation, where lumen volume changes can impact epithelial shape, via both direct mechanical (passive) and indirect mechano-sensitive (active) mechanisms. We show how mechano-sensitive feedbacks on cytoskeletal tension generically give rise to morphological bistability, where both bulged (open) and budded (closed) crypt states are possible and dependent on the history of volume changes. We experimentally test key modelling assumptions via biophysical and pharmacological experiments, allowing us to quantitatively demonstrate how bistability can explain several paradoxical experimental observations, such as the importance of the timing of lumen shrinkage and robustness of the final morphogenetic state to mechanical perturbations. This suggests that bistability, arising from feedbacks between cellular tensions and fluid pressure, could be a general mechanism to coordinate multicellular shape changes in developing systems

Andrew Holle
National University of Singapore, Singapore

Ayelet Lesman
Tel Aviv University, Israel

Pavel Levkin
Karlsruhe Institute of Technology (KIT), Germany

Roberto Mayor
University College London, UK

Matthias Merkel
Université Aix-Marseille, France

Aleksandr Ovsianikov
Technical University Wien, Austria

 

Aurélien Roux
Université de Genève, Switzerland

Motomu Tanaka
Heidelberg University, Germany

Danijela Vignjevic 
Institut Curie Paris, France

Jennifer Young
National University of Singapore, Singapore