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Pulsations and flows: controlling two collective modes in epithelial monolayers


Title : Pulsations and flows: controlling two collective modes in epithelial monolayers.
Speaker : Dr. Raghavan Thiagarajan, postdoctoral fellow at re NEW, Copenhagen.
Date : 06/09/2022, 05:30 PM , Online Mode.


During embryonic development, tissues elongate, contract, flow and oscillate to sculpt morphogenesis. Although these tissue level dynamics are known, the physical mechanisms at the cellular level are unclear. Moreover, investigations on tissue behavior usually focuses on one type of cell dynamics and use unique theoretical approaches for each study. Here, we overcome this issue by using an epithelial cell culture system for studying two distinct dynamics, applying the same theoretical approach. We show that a single epithelial monolayer of MDCK cells can exhibit two types of local tissue dynamics: pulsations and long range coherent flows. We find that these motions can be controlled by internal and external cues such as actomyosin organisation, and friction modulation of the substrate, through quantitative imaging, cytoskeletal inhibitors, micro patterning and micro fabricated structures. We further demonstrate with a unified vertex model that both behaviors depend on the competition between velocity alignment and random diffusion of cell polarization. When alignment and diffusion are comparable, a pulsatile flow emerges, whereas the tissue undergoes long-range flows when velocity alignment dominates. Taken together, we show that in a system that presents two different dynamics, substrate friction, actomyosin distributions, and cell polarization kinetics are essential in modulating their characteristics. These insights can be useful in characterizing the complexities in cellular morphogenesis and the physical parameters involved in tissue-level organization.

CV / Bios ketch:

My scientific interest lies in understanding the role of physical phenomena (mechanical forces, pattern formation, self-organization) during embryonic development and in exploring ways to quantify developmental processes. This motivation comes from my cross-disciplinary background in engineering and fascination with biological systems. After a short exposure to computational work during Bachelor’s studies at SASTRA University, India, I shifted my focus to experimental optics and imaging. For my Master’s project, I joined the group of Prof. VM Murukeshan at NTU, Singapore, to assemble a digital-in-line holography setup. I applied this system for the fast 3D imaging of nanoparticle dynamics in mammalian cells to evaluate their therapeutic applications. Following this, I joined Prof. Daniel Riveline’s lab at IGBMC & ISIS, Strasbourg to study the process of self-organization at different scales. At the molecular scale, I determined how an ensemble of actomyosin motors generate constriction force during cytokinesis in fission yeast and mammalian cells. At the scale of single-cell, I dissected the mechanism of how multiple filopodia formation lead to directed migration in mouse fibroblast cells. Finally, at the tissue scale, I worked on the emergence and regulation of spontaneous oscillations and flows in MDCK epithelial monolayers. Collectively, these projects led to high-impact publications. Particularly, the work on cytokinetic ring constriction has a strong recognition in the biophysics field as it dissects the function of self-organization in the mechanical force generation. Additionally, I was actively involved in engineering innovative microfabricated structures and in testing novel bio compounds (synthetic polyamines) that can increase actin polymerization dynamics. Through these projects, I have built a diverse set of skills across different model systems, imaging methods, and engineering techniques. Importantly, I have gained extensive training in quantitative image analysis strategies. Currently, I am a Postdoc in Prof. Jakub Sedzinski’s lab at re NEW, Copenhagen. Here, I am studying the role of mechanical forces, and quantifying sub cellular organisation using high-resolution and high-temporal imaging, during mucociliary epithelial morphogenesis in Xenopus embryos.