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.
Heidelberg University, 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.
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, 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.
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