Tissue self organisation and development

Leader: E. Loiseau, E. Gehrels, V. Viasnoff, A. Viallat


Topology and dynamics of ciliated epitheliums.

Principal investigators: E. Loiseau, A. Viallat,

PhD student: A. Baby

From swimming microorganisms to major organs including the brain, the respiratory system and the reproductive tracts, ciliated cells are ubiquitous in living systems. Their multiple active cilia continuously consume chemical energy and beat unidirectionally to ensure biological functions of motility, washing and transport. Strikingly, depending on the organ considered, the morphology of the cilia, the distribution of cilia at the cell level as well as the distribution of multiciliated cells at the tissue level vary greatly. This raises the general questions: How does millions of active cilia coordinate their beatings to generate a coherent flow over macroscopic distances? Can we predict an optimal ciliary configuration to generate a flow whose topology is adapted to a specific biological function? How does it compare with the biological system? To answer these questions, we combine active matter physics with quantitative biology and computational fluid mechanics.

The respiratory tract, fluid flow patterns and biological function

The respiratory tract is protected by mucus, a complex fluid transported along the epithelial surface by the coordinated beating of millions of microscopic cilia, hence the name of mucociliary clearance. Its impairment is associated with all severe chronic respiratory diseases. we show on in-vitro reconstituted human bronchial epithelia that mucus swirls and circular orientational order of the underlying ciliary beats emerge and grow during ciliogenesis, until a macroscopic mucus transport is achieved for physiological ciliary densities. By establishing that the macroscopic ciliary-beat order is lost and recovered by removing and adding mucus, respectively, we demonstrate that cilia–mucus hydrodynamic interactions govern the collective dynamics of ciliary-beat directions. We developed a two-dimensional model that predicts a phase diagram of mucus transport in accordance with the experiments. See publication Nature Physics 2020

Surface of the embryonic skin of the amphibian Xenopus laevis

This surface contains ciliated cells, distributed on the nodes of a surprisingly regular network, bear beating cilia that generate a flow along the embryo. These ciliated cells disappear when the embryo’s immune system becomes functional, thus suggesting that the flow’s function is to eliminate surrounding pathogens. Is the specific cellular distribution essential for an effective washing out of bacteria from the embryo’s skin? What happens if this distribution is disturbed? We cultivate skin explants in-vitro on which we can modify the spatial distribution of ciliated cells. We determine the 3D flows over the skin surface at the tissue scale by using Particle Image Velocimetry techniques. We combine experimental approaches and computational fluid dynamics to understand the intricate interplay between spatial distribution, coordination of beat direction and cilia own dynamics, responsible for the generation of a protective flow around the embryo that washes out external pathogens.

Longitudinal to Transverse Metachronal Wave Transitions in an In Vitro Model of Ciliated Bronchial Epithelium

Myriads of cilia beat on ciliated epithelia, which are ubiquitous in life. When ciliary beats are synchronized, metachronal waves emerge, whose direction of propagation depends on the living system in an unexplained way. We show on a reconstructed human bronchial epithelium in vitro that the direction of propagation is determined by the ability of mucus to be transported at the epithelial surface. Numerical simulations show that longitudinal waves maximize the transport of mucus while transverse waves, observed when the mucus is rigid and still, minimize the energy dissipated by the cilia. Phys Rev Lett 2022


Tissue mechanics and dynamics during Drosophila morphogenesis.

Principal investigator: E. Gehrels

During embryonic development, tissues flow and fold to create the complex form required to support life. For tissues to maintain integrity while undergoing large flows, the composing cells need to dynamically rearrange to allow the tissue to act as a fluid instead of a solid. It has been proposed that dynamic fluctuations in cell-shape could facilitate cell rearrangement and therefore fluidization of the tissue, but there is a lack of experimental evidence to support or refute this hypothesis. Moreover, is unknown if such fluctuations would arise from passive thermal effects or from active, energy-consuming processes in the cells.

Our research utilizes live-imaging of Drosophila embryos to quantify cellular dynamics and correlate them to tissue flow. We combine techniques from biology and physics to (1) examine the role that cell-scale fluctuations play in tissue fluidization, (2) measure how these fluctuations depend on energy consumption within the cell, and (3) uncover whether changes in tissue fluidization result from thermal effects, or from non-equilibrium (energy-consuming) processes. To quantify and interpret the results from our experiments, we relate them to biophysical models of tissue mechanics/ dynamics and to non-equilibrium statistical mechanics of living systems.



Transit Time Theory for a Droplet Passing through a Slit in Pressure-Driven Low Reynolds Number Flows

Spencer W Borbas, Kevin Shen, Catherine Ji, Annie Viallat, Emmanuèle Helfer, Zhangli Peng

Micromachines 14:2040 (2023)10.3390/mi14112040

Classification of red cell dynamics with convolutional and recurrent neural networks: a sickle cell disease case study

Maxime Darrin, Ashwin Samudre, Maxime Sahun, Scott Atwell, Catherine Badens, Anne Charrier, Emmanuèle Helfer, Annie Viallat, Vincent Cohen-Addad, Sophie Giffard-Roisin

Scientific Reports 13:745 (2023)10.1038/s41598-023-27718-w

Curvature gradient drives polarized tissue flow in the Drosophila embryo

Emily W Gehrels, Bandan Chakrabortty, Marc-Eric Perrin, Matthias Merkel, Thomas Lecuit

Proceedings of the National Academy of Sciences of the United States of America 120 (2023)10.1073/pnas.2214205120

Enhanced cell viscosity: a new phenotype associated with lamin A/C alterations

Cécile Jebane, Alice-Anaïs Varlet, Marc Karnat, Lucero Hernandez- Cedillo, Amélie Lecchi, Frédéric Bedu, Camille Desgrouas, Corinne Vigouroux, Marie-Christine Vantyghem, Annie Viallat, Jean-François Rupprecht, Emmanuèle Helfer, Catherine Badens

iScience 26:107714 (2023)10.1016/j.isci.2023.107714

Physical mechanisms of red blood cell splenic filtration

Alexis Moreau, François Yaya, Huije Lu, Anagha Surendranath, Anne Charrier, Benoit Dehapiot, Emmanuèle Helfer, Annie Viallat, Zhangli Peng

Proceedings of the National Academy of Sciences of the United States of America (2023)10.1101/2023.01.10.523245

Analytical theory for a droplet squeezing through a circular pore in creeping flows under constant pressures

Zhengxin Tang, François Yaya, Ethan Sun, Lubna Shah, Jie Xu, Annie Viallat, Emmanuèle Helfer, Zhangli Peng

Physics of Fluids 35:082016 (2023)10.1063/5.0156349


Dynamics of Individual Red Blood Cells Under Shear Flow: A Way to Discriminate Deformability Alterations

Scott Atwell, Catherine Badens, Anne Charrier, Emmanuèle Helfer, Annie Viallat

Frontiers in Physiology 12 (2022)10.3389/fphys.2021.775584

Mechanochemical Principles of Spatial and Temporal Patterns in Cells and Tissues

Anaïs Bailles, Emily Gehrels, Thomas Lecuit

Annual Review of Cell and Developmental Biology 38 (2022)10.1146/annurev-cellbio-120420-095337

Programming Directed Motion with DNA-Grafted Particles

Emily W Gehrels, W. Benjamin Rogers, Zorana Zeravcic, Vinothan N Manoharan

ACS Nano 16:9195-9202 (2022)10.1021/acsnano.2c01454

Longitudinal to Transverse Metachronal Wave Transitions in an In Vitro Model of Ciliated Bronchial Epithelium

Olivier Mesdjian, Chenglei Wang, Simon Gsell, Umberto D’ortona, Julien Favier, Annie Viallat, Etienne Loiseau

Physical Review Letters 129:038101 (2022)10.1103/PhysRevLett.129.038101

Lrrcc1 and Ccdc61 are conserved effectors of multiciliated cell function

Aude Nommick, Camille Boutin, Olivier Rosnet, Claire Schirmer, Elsa Bazellières, Virginie Thomé, Etienne Loiseau, Annie Viallat, Laurent Kodjabachian

Journal of Cell Science (2022)10.1242/jcs.258960


Mechanical adaptation of monocytes in model lung capillary networks

Jules Dupire, Pierre-Henri P Puech, Emmanuèle Helfer, Annie Viallat

Proceedings of the National Academy of Sciences of the United States of America 117:14798 (2020)

Hydrodynamic model of directional ciliary-beat organization in human airways

Simon Gsell, Etienne Loiseau, Umberto D’ortona, Annie Viallat, Julien Favier

Scientific Reports 10 (2020)10.1038/s41598-020-64695-w

Active mucus–cilia hydrodynamic coupling drives self-organization of human bronchial epithelium

Etienne Loiseau, Simon Gsell, Aude Nommick, Charline Jomard, Delphine Gras, Pascal Chanez, Umberto D’ortona, Laurent Kodjabachian, Julien Favier, Annie Viallat

Nature Physics (2020)10.1038/s41567-020-0980-z


Self-organization of red blood cell suspensions under confined 2D flows

Cécile Iss, Dorian Midou, Alexis Moreau, Delphine Held, Anne Charrier, Simon Mendez, Annie Viallat, Emmanuèle Helfer

Soft Matter (2019)10.1039/C8SM02571A


Reconstitution of composite actin and keratin networks in vesicles

J. Deek, R. Maan, E. Loiseau, R. Bausch

Soft Matter 14:1897-1902 (2018)10.1039/c7sm00819h

Using DNA strand displacement to control interactions in DNA-grafted colloids

Emily W. Gehrels, W. Benjamin Rogers, Vinothan N. Manoharan

Soft Matter 14:969-984 (2018)10.1039/C7SM01722G

Spatiotemporal organization of cilia drives multiscale mucus swirls in model human bronchial epithelium

Mustapha-Kamel Khelloufi, Etienne Loiseau, Marc Jaeger, Nicolas Molinari, Pascal Chanez, Delphine Gras, Annie Viallat

Scientific Reports 8:2447 (2018)10.1038/s41598-018-20882-4

Adhesion of Active Cytoskeletal Vesicles

Renu Maan, Etienne Loiseau, Andreas Bausch

Biophysical Journal 115:2395-2402 (2018)10.1016/j.bpj.2018.10.013

When giant vesicles mimic red blood cell's dynamics: swinging of two-phase vesicles in shear flow

Simon Tusch, Etienne Loiseau, Al-Hair Al-Halifa, Kamel Khelloufi, Emmanuèle Helfer, Annie Viallat

Physical Review Fluids 3 (2018)10.1103/PhysRevFluids.3.123605


High Aspect Ratio Sub-Micrometer Channels Using Wet Etching: Application to the Dynamics of Red Blood Cell Transiting through Biomimetic Splenic Slits

Priya Gambhire, Scott Atwell, Cécile Iss, Frédéric Bedu, Igor Ozerov, Catherine Badens, Emmanuèle Helfer, Annie Viallat, Anne Charrier

Small 13:1700967 (2017)10.1002/smll.201700967


Shape remodeling and blebbing of active cytoskeletal vesicles

Etienne Loiseau, Jochen A. M. Schneider, Felix C. Keber, Carina Pelzl, Gladys Massiera, Guillaume Salbreux, Andreas R. Bausch

Science Advances 2:UNSP e1500465 (2016)10.1126/sciadv.1500465


• ANR, 2023-27 Natural and assisted airways drainage in COPD