Symposium Series Physics and Medicine (3)
Pressure, density, elasticity are classical physical properties, which are required to fully describe the processes in human cell assemblies – for example, to distinguish tumours from healthy tissue or to stimulate the regrowth of nerve cells. These examples illustrate how physics can provide new stimuli for basic medical research.
Today, modern physical methods and physical thinking are being transferred towards physiological application worldwide. In order to promote the exchange between different researchers and working groups, the Max Planck Zentrum für Physik und Medizin is starting a new series of public mini-symposia, in which two to three scientists from North America, Europe or Asia will present their work virtually. The series starts on March 10th, with further symposia planned for March 11th and 19th — and more to follow…
To take part in the symposia, please register for MPL's scientific lectures newsletter (please ensure that you tick the "scientific lecture" checkbox). We will send the Zoom links about one hour before the symposium starts.
The schedule for Friday, March 19th in detail:
14:00 - 14:05 Welcome
14:05 - 14:50 Timothy Saunders, MBI Singapore: "Mechanical proofreading as a mechanism for ensuring robust cell matching during cardiogenesis"
Abstract:
Actomyosin networks are essential for regulating cell and tissue morphogenesis. These networks are highly dynamics, enabling cells to undergo a wide range of actions. Yet, how cells integrate the different mechanical stimuli to accomplish complicated tasks in vivo remains unclear. We utilise the process of cell matching in the Drosophila heart as a simple system that enables us to explore this problem. During heart formation, selective filopodia-binding adhesions between opposing cells ensure the cells align precisely. Intriguingly, non-muscle Myosin II clusters oscillate within cardioblasts with a period of ~4-min. The filopodia dynamics, such as protrusion, retraction, and binding stabilization, are correlated with the periodic localization of Myosin II clusters at the cell leading edge. Perturbing the patterns of Myosin II activity alters the filopodia dynamics and results in poorly aligned heart cells. Combining our experimental work, we propose a mechanical proofreading mechanism, where oscillations of Myosin II within cardioblasts periodically probe filopodia adhesion strength and ensure correct cell-cell connection formation. Building on our above work, we have developed an equilibrium energy model to simulate how cell matching can occur with subcellular precision. A single parameter – encapsulating the competition between selective cell adhesion and cell elasticity – can reproduce experimental observations of cell alignment in the Drosophila embryonic heart. This demonstrates that adhesive differences between cells (in the case of the heart, mediated by filopodia interactions) are sufficient to drive cell matching without requiring cell rearrangements. The model can explain observed matching defects in mutant conditions and when there is significant biological variability. We also demonstrate that a dynamic vertex model gives results consistent with the equilibrium energy model. Overall, this work shows that equilibrium energy considerations are consistent with observed cell matching in cardioblasts, and has potential application to other systems, such as neuron connections and wound repair.
— 10 min break —
15:00 - 15:45 Thomas Angelini, University of Florida: "How to investigate cell behavior in 3D? 3D print your experiments"
Abstract:
The remarkable differences between cells grown on plates and cells in vivo or in 3D culture are well-known. At the physical level, cell shape, structure, motion, and mechanical behavior in 3D are totally different from those in the dish and are far less explored. At the molecular level, cells grown in monolayers exhibit gene expression profiles that do not correlate or are anticorrelated with those of cells grown in 3D culture or xenograft animal models. However, our understanding of cell biology has been heavily shaped by the culture plate, whether viewed through the lens of gene expression profiles, signaling pathways, morphological characterization, or mechanical behaviors. Closing this major gap between 2D in vitro culture and in vivo biology requires a tunable and flexible method for creating 3D cell assemblies and performing experiments on cells in 3D environments. In this talk I will describe how we use a bioprinter in combination with a 3D culture medium made from jammed microgels to perform a wide range of 3D experiments. I will demonstrate this experimental platform’s ability to print structures made from multiple cell types or extracellular matrix with predictable feature sizes down to the scale of a few cell bodies. I will also present data from numerous types of experiments performed in 3D, designed to explore collective cell behavior and cell-cell interactions. For example, recent results will be presented from a 3D immunotherapy model in which we investigate how antigen-specific T cells attack 3D printed brain tumoroids. Our results demonstrate that, in parallel to pursuing the long-standing goals shared by those within the 3D bioprinting field, the current state of bioprinting technology can be leveraged to perform a wide diversity of experiments.
— 10 min break —
15:55 - 16:40 Kandice Tanner, NIH, Bethesda: "Microenvironment regulation of metastasis"
Abstract:
In the event of metastatic disease, emergence of a lesion can occur at varying intervals from diagnosis and in some cases following successful treatment of the primary tumor. Genetic factors that drive metastatic progression have been identified, such as those involved in cell adhesion, signaling, extravasation and metabolism. However, organ specific biophysical cues may be a potent contributor to the establishment of these secondary lesions. We combine a novel preclinical model of metastasis with that of optical tweezer based active microrheology to elucidate the role of tissue biophysical properties of in the establishment of metastatic lesions in vivo. Specifically, I will discuss our efforts to determine what physical cues influence disseminated tumor cells in different organ microenvironments using in vitro and in vivo preclinical models such as 3D culture systems and zebrafish.
