Physics of Form and Flows
Physics of Form and Flows
from quantitative biology to physical principles
from quantitative biology to physical principles
Arghyadip Mukherjee,Dr.rer.nat.
Junior Research Chair@ LPENS & QBio-PariSante Campus
Theoretical Physicist trying to unravel principles of morphogenesis
I have always been fascinated with the diversity of shapes in the natural world around us. Biological matter is unique because it is soft and active -- with the ability to deform, move, mould into complex architectures. But unlike inanimate objects, living shapes serve specific functions.
Understanding how a collection of cells lead to formation of a variety of functional multicellular structures/tissues is the central theme of my research.
I use theoretical concepts of active matter physics to identify underlying principles that govern the organisation and dynamics of living tissues. Such ideas are formulated with simple mathematical models. Theoretical approaches for me represent not only a way to capture the true essence of a biophysical phenomena but also an instrument to gain novel quantitative insights.
For a light-hearted reading see this profile piece on my research on the ENS news here.
Resumé
Experience and education:March 2022- now QBio Junior Research Chair at the Ecole Normale Supérieure and QBio initiative within the PariSante CampusMarch 2022- now Invited researcher at the College de France, ParisMay 2021- Feb 2022 Research Fellow with Jan Brugués at MPICBGSept 2016- April 2021 PhD student with Frank Jülicher at MPIPKSJuly 2015- July 2016 BS thesis with Shashi Thutupalli at NCBSAug 2012- July 2016 BS (Research) in Physics at Indian Institute of ScienceFellowships and support:Joachim-Herz Foundation Add-On Fellowship in Systems Biology 2017-2019
KVPY Fellowship, Govt.of India 2011-2016
Research
"Physics is the idea that, with effort and ingenuity, the world around us is understandable."
- John Hopfield
Effective theory of epithelial morphogenesis
We formulate coarse-grained theories of epithelial mechanics starting from cell-based vertex models. As a result the theory is captured by only a few effective parameters which are functionals of the cellular paramters. This approach allows a field theoretic view of epithelial morphogenesis and leads to simple, disprovable and quantitative insights/predictions. (See for example Ishihara*,Mukherjee* et.al. Nat.Phys. 2022)
Type of research: Collaborative between theory and experiments.
Ordering dynamics of cytoskeletal composites
The syncytial stage of the early embryo of Drosophila and Zebrafish, shows intricate order in the organisation of aster and nuclei despite the absence of cell boundaries. How such ordered structures are stable however remains a mystery. Using the theory of active polar gels we derive a model for a free monopolar microtubule aster discussing transport of material, size control and effective interactions with a neighbouring aster. Starting from this we formulate a macroscopic theory of active defects and find how large-scale two dimensional pseudo-ordering can emerge.
In Experimental collaboration with Melissa Rinaldin and Jan Brugués.
Type of research: Collaborative between theory and experiments.
Hydraulics of polarized tissues
Epithelial tissues have clear apico-basal polarity and often encapsulate a fluid-filled cavity called lumen which mediate chemical signalling. The lumen is nucleated by pumping activity of cells. In tubular lumens such pumping can give rise to large scale flows and lead to interesting interplay of fluid mechanics and cell mechanics. See for example Chartier* and Mukherjee* et.al. Nature Physics 2021 where hydraulic exchanges drive the fate of oocytes.
We also recently discovered a mechanochemical interplay that gives rise to excitable dynamics of intercellular fluid pockets in the mouse blastocyst. This excitable dynamics interacts with embryo topolgy and affects lumen coarsening (Schliffka et al. BiorXiv 2023).
Type of research: Collaborative between theory and experiments.
Shape of cells in curved thin tissues
The understanding of cell shapes within a tissue is typically limited to simple tissue geometries. Cell shapes often depict the distribution of forces within the tissues and the underlying geometry. For example the underlying curvature can affect cell shape (see Left Figure shaded regions green and purple). I develop geometric techniques and theories to understand cell shapes in non-euclidean geometries.
In Experimental Collaboration with Keisuke Ishihara at Uni. Pittsburgh, USA
Type of research: Collaborative between theory and experiments.
Evolutionary dynamics in syncytial structures
I want to understand how multicellularity can arise and be stable under primitive conditions where multiple nuclei share cytoplasm. Similar questions exist in the case of metabolic sharing and evolution of cooperation however the phenomenological ideas of evolutionary dynamics neglect the physical mechanisms that must mediate interactions between cells. To understand how physical forces affect the evolution and stability of cooperative structures I am develop theories starting from the explicit mechanics and hydrodynamics of cellular interactions. Using coarse-graining I derive theories of effective evolutionary dynamics which allows a physical interpretation of cooperative effects.
Type of research: Theoretical, at the interface of soft-matter physics and evolutionary game theory
Selected Publications
papers are hyperlinked and please click on the orange text to visit the publications.
*indicates equal contribution first-author
Markus F. Schliffka, Julien G. Dumortier, Diane Pelzer, Arghyadip Mukherjee*, Jean-Léon Maître*
BiorXiv 2023/ in review
During preimplantation development, mouse embryos form a fluid-filled lumen, which sets their first axis of symmetry. Pressurized fluid breaks open cell-cell contacts and accumulates into pockets, which gradually coarsen into a single lumen. During coarsening, the adhesive and contractile properties of cells are thought to guide intercellular fluid (IF) but what cell behavior may control fluid movements is unknown. Here, we report large fluid-filled spherical membrane intrusions called inverse blebs growing into cells at adhesive contacts. At the onset of lumen coarsening, we observed hundreds of inverse blebs throughout the embryo, each dynamically filling with IF and retracting within a minute. We find that inverse blebs grow due to pressure build-up resulting from luminal fluid accumulation and cell-cell adhesion, which locally confines fluid. Inverse blebs then retract due to actomyosin contraction, which effectively redistributes fluid within the intercellular space. Importantly, inverse blebs show topological specificity and only occur at contacts between two cells, not at contacts formed by multiple cells, which essentially serve as fluid sinks. Manipulating the topology of the embryo reveals that, in the absence of sinks, inverse blebs pump fluid into one another in a futile cycle. We propose that inverse blebs operate as hydraulic pumps to promote luminal coarsening, thereby constituting an instrument used by cells to control fluid movement.
K. Ishihara* , A. Mukherjee*, E.Gromberg , J. Brugues´ , Elly M. Tanaka , Frank Jülicher Nature Physics 2022
Animal organs exhibit complex topologies involving cavities and tubular networks, which underlie their form and function. However, how topology emerges during organ morphogenesis remains elusive. Here, we combine tissue reconstitution and quantitative microscopy to show that trans and cis epithelial fusion govern tissue topology and shape. These two modes of topological transitions can be regulated in neuroepithelial organoids, leading to divergent topologies. The morphological space can be captured by a single control parameter which is analogous to the reduced Gaussian rigidity of an epithelial surface. Finally, we identify a pharmacologically accessible pathway that regulates the frequency of trans and cis fusion, and demonstrate the control of organoid topology and shape. The physical principles uncovered here, provide fundamental insights into the self-organization of complex tissues.
N.T. Chartier*, A. Mukherjee*, J. Pfanzelter*, S Fürthauer, B.T. Larson, A.W. Fritsch, R. Amini, M. Kreysing, F. Jülicher & S.W. Grill Nature Physics 2021
Oocytes are large cells that develop into an embryo upon fertilization. As interconnected germ cells mature into oocytes, some of them grow—typically at the expense of others that undergo cell death. We present evidence that in the nematode Caenorhabditis elegans, this cell-fate decision is mechanical and related to tissue hydraulics. An analysis of germ cell volumes and material fluxes identifies a hydraulic instability that amplifies volume differences and causes some germ cells to grow and others to shrink, a phenomenon that is related to the two-balloon instability. Shrinking germ cells are extruded and they die, as we demonstrate by artificially reducing germ cell volumes via thermoviscous pumping6. Our work reveals a hydraulic symmetry-breaking transition central to the decision between life and death in the nematode germline.
A. Jain, V. Ulman, A. Mukherjee, M. Prakash, M.B. Cuenca, L.G. Pimpale, S. Münster, R. Haase, K.A. Panfilio, F. Jug, S.W. Grill, P. Tomancak & A. Pavlopoulos
Nature Communications 2020
Many animal embryos pull and close an epithelial sheet around the ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the spreading epithelium is mechanically stressed and this stress needs to be released. Here we show that during extraembryonic tissue (serosa) epiboly in the insect Tribolium castaneum, the non-proliferative serosa becomes regionalized into a solid-like dorsal region with larger non-rearranging cells, and a more fluid-like ventral region surrounding the leading edge with smaller cells undergoing intercalations. Our results suggest that a heterogeneous actomyosin cable contributes to the fluidization of the leading edge by driving sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.
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