TEAM

Physical approaches to cell dynamics and tissue morphogenesis

Group leader : P.F. Lenne

Our group aims at determining how mechanical and physical interactions are organized at cell surfaces in vivo and how these interactions are processed to produce cell and tissue responses.

FOR BEGINNERS

The making of an organism relies on interactions at cell surfaces and communication between cells.  How are mechanical and physical interactions organized at cell surfaces in vivo ? How are these interactions processed to produce cell and tissue responses? We tackle these questions by combining physical and genetic/molecular approaches. In particular we study how cell behaviours such as cell shape changes and cell polarity emerge from the mesoscopic (between the microscopic and macroscopic scales) properties of cell surface and interfaces in vivo.

Cadherin Clusters at adherens junctions.

Our work is multidisciplinary and integrates physical/mechanical and molecular/genetic approaches. In particular we develop microscopes to observe subcellular structures at high resolution, measure molecular interactions and probe the local mechanics of cells. We also use modelling to make quantitative and falsifiable predictions, which we test experimentally. Modelling is also a guide for new experiments. We hope that such approaches may shed light on fundamental mechanisms of Life and will be useful for medical applications (imaging and tissue engineering).

FOR SPECIALISTS

Our group aims at determining how mechanical and physical interactions are organized at cell surfaces in vivo and how these interactions are processed to produce cell and tissue responses. To tackle these broad questions, we focus on two aspects of tissue morphogenesis, namely cell polarization and force transmission in fields of cells. More specifically we study:

(1) the assembly and dynamics of adhesion complexes at cell interfaces in vivo ;

(2) the mechanics of cell interfaces and force transmission in a tissue ;

(3) the molecular interactions during tissue polarization in vivo.

We are using Drosophila and C. Elegans as models systems to address questions (1-2) and question (3), respectively. The originality of our project relies in the integration of both physics (optics/microscopy/mechanics/modelling) and experimental biology to study quantitatively tissue morphogenesis.

1.    Assembly and dynamics of adhesion complexes at cell interfaces in vivo 

Facets of the Drosophila retina

Cell-cell adhesion requires the formation of finite clusters where adhesion is concentrated. Moreover, subcellular tensile forces are coupled to and transmitted at adhesive clusters. These clusters are mechanically regulated. Thus, understanding the organization/dynamics of such clusters is an essential step. We study quantitatively the supramolecular organisation of cadherins (E- and N-cadherin) in the early embryonic epithelium and in the pupal retina of Drosophila by combining super-resolution imaging, dynamic Imaging and modeling.

2.    Mechanics of cell interfaces and force transmission in a tissue

Légende

Simulations of clusters made of trivalent particles.

During the formation of tissues, cells divide, change their shape and their position, or die.
This small set of mechanisms determines the shape and the size of tissues. While we know a great deal about the genes which orchestrate these mechanisms, we do not know much about the physical forces which ‘sculpt’ the tissues. What are the forces that cells generate to shape the tissues? In collaboration with the group of Thomas Lecuit, we have recently shown that force generators act at cell surfaces to produce local remodeling of cell contacts (Rauzi et al, 2008, 2010).

Yet, how coupling through adhesive clusters change and regulate the mechanics of tissues and therefore force propagation is poorly understood. Using micromanipulation (e.g. optical tweezers) and force sensors, we try to tackle this question.

3. Quantitative map of molecular interactions during tissue polarization in vivo

C. elegans embryo imaging using light sheet microscopy

C. elegans embryo imaging using light sheet microscopy

How do animal tissues acquire specific polarity axes during morphogenesis? While gradients of signaling molecules have been suggested to play a role in this process, our understanding of the mechanisms underlying tissue polarization is still very partial. In particular we lack quantitative data on the behaviour and interactions between the molecular players, such as ligands and their receptors, during the polarization process in vivo. We recently teamed up with the group of Vincent Bertrand (IBDM) to tackle this question in C. Elegans.

Light sheet microscope

Light sheet microscope

By combining quantitative Imaging and genetic perturbation, we aim at mapping the distribution/dynamics of Wnt ligands, of receptors and of their interactions during the polarisation of a tissue in vivo


Main publications

PUBLICATION

Direct laser manipulation reveals the mechanics of cell contacts in vivo.

Bambardekar K, Clément R, Blanc O, Chardès C, Lenne PF.
Proc Natl Acad Sci U S A. 2015 Feb 3;112(5):1416-21. PMID: 25605934

PUBLICATION

Principles of E-Cadherin Supramolecular Organization In Vivo.

Truong Quang BA, Mani M, Markova O, Lecuit T, Lenne PF.
Curr Biol. 2013 Oct 29. pii: S0960-9822(13)01131-7. PMID:24184100

PUBLICATION

Bond flexibility and low valence promote finite clusters of self-aggregating particles.

Markova O, Alberts J, Munro E, Lenne PF.
Phys Rev Lett. 2012 Aug 17;109(7):078101. PMID: 23006403

PUBLICATION

Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis.

Rauzi M, Verant P, Lecuit T, Lenne PF.
Nat Cell Biol. 2008 Dec;10(12):1401-10. PMID: 18978783
Other publications

PUBLICATION

Calcium Spikes in Epithelium: study on Drosophila early embryos.

Markova O, Sénatore S, Chardès C, Lenne PF.
Sci Rep. 2015 Jul 22;5:11379. PMID: 26198871

PUBLICATION

Superresolution measurements in vivo: imaging Drosophila embryo by photoactivated localization microscopy.

Truong Quang BA, Lenne PF.
Methods Cell Biol. 2015;125:119-42. PMID: 25640427

PUBLICATION

Probing cell mechanics with subcellular laser dissection of actomyosin networks in the early developing Drosophila embryo.

Rauzi M, Lenne PF.
Methods Mol Biol. 2015;1189:209-18. PMID: 25245696

PUBLICATION

Clustering of low-valence particles: structure and kinetics.

Markova O, Alberts J, Munro E, Lenne PF.
Phys Rev E Stat Nonlin Soft Matter Phys. 2014 Aug;90(2):022301. PMID: 25215732

PUBLICATION

Setting-up a simple light sheet microscope for in toto imaging of C. elegans development.

Chardes C., Melenec P., Bertrand V. And Lenne P.F.
J Vis Exp. 2014 May 5;(87). PMID: 24836407

PUBLICATION

Membrane microdomains: from seeing to understanding.

Truong-Quang BA, Lenne PF.
Front Plant Sci. 2014 Feb 18;5:18. PMID: 24600455

PUBLICATION

Cortical forces in cell shape changes and tissue morphogenesis.

Rauzi M, Lenne PF.
Curr Top Dev Biol. 2011;95:93-144 PMID: 21501750

PUBLICATION

Calcium signaling in developing embryos: focus on the regulation of cell shape changes and collective movements.

Markova O, Lenne PF.
Semin Cell Dev Biol. 2012 May;23(3):298-307. PMID: 22414534

PUBLICATION

FCS diffusion laws in two-phase lipid membranes: determination of domain mean size by experiments and Monte Carlo simulations.

Favard C, Wenger J, Lenne PF, Rigneault H.
Biophys J. 2011 Mar 2;100(5):1242-51. PMID: 21354397

PUBLICATION

Force generation, transmission, and integration during cell and tissue morphogenesis.

Lecuit T, Lenne PF, Munro E.
Annu Rev Cell Dev Biol. 2011;27:157-84. PMID: 21740231

PUBLICATION

Planar polarized actomyosin contractile flows control epithelial junction remodelling.

Rauzi M, Lenne PF, Lecuit T.
Nature. 2010 Dec 23;468(7327):1110-4. PMID: 21068726

PUBLICATION

Probing cell-surface dynamics and mechanics at different scales.

Lenne PF.
Histochem Cell Biol. 2009 Sep;132(3):247-52. PMID: 19633983

PUBLICATION

Fluorescence fluctuations analysis in nanoapertures: physical concepts and biological applications.

Lenne PF, Rigneault H, Marguet D, Wenger J.
Histochem Cell Biol. 2008 Nov;130(5):795-805. PMID: 18800223

PUBLICATION

Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation.

Lasserre R, Guo XJ, Conchonaud F, Hamon Y, Hawchar O, Bernard AM, Soudja SM, Lenne PF, Rigneault H, Olive D, Bismuth G, Nunès JA, Payrastre B, Marguet D, He HT.
Nat Chem Biol. 2008 Sep;4(9):538-47. PMID: 18641634

PUBLICATION

A two-tiered mechanism for stabilization and immobilization of E-cadherin.

Cavey M, Rauzi M, Lenne PF, Lecuit T.
Nature. 2008 Jun 5;453(7196):751-6. PMID: 18480755

PUBLICATION

Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis.

Lecuit T, Lenne PF.
Nat Rev Mol Cell Biol. 2007 Aug;8(8):633-44. PMID: 17643125

PUBLICATION

Dynamic molecular confinement in the plasma membrane by microdomains and the cytoskeleton meshwork.

Lenne PF, Wawrezinieck L, Conchonaud F, Wurtz O, Boned A, Guo XJ, Rigneault H, He HT, Marguet D.
EMBO J. 2006 Jul 26;25(14):3245-56. PMID:16858413

PUBLICATION

Enhancement of single-molecule fluorescence detection in subwavelength apertures.

Rigneault H, Capoulade J, Dintinger J, Wenger J, Bonod N, Popov E, Ebbesen TW, Lenne PF.
Phys Rev Lett. 2005 Sep 9;95(11):117401. PMID:16197045

Interactions

IBDM
NATIONAL
  • Hervé Rigneault, Mosaic Team, Institut Fresnel, Marseille
INTERNATIONAL
  • Edwin Munro, University of Chicago
  • Madhav Mani, KITP, University of Santa Barbara

Lab Twitter


Funding

ANR

FRM

Labex

Logo-ATIP-AVENIRBioimaging

Members more

monika Ludanyi   Eunice hoyee Chan Claire Chardes Pruthvi Chavadimane Shivakumar Raphael Clement Edith Laugier olivier Loison Pierre Mangeol Pierre Recouvreux
Pierre-françois Lenne
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Pierre-françois Lenne

Researcher

Pierre-François studied physics at the University of Paris and Ecole Normale Supérieure of Paris, France, before completing his PhD in soft matter physics at the University of Grenoble, France. After postdoctoral research in the cell biology and biophysics unit of EMBL (Heidelberg, Germany), he joined the National Centre for Scientific Research (CNRS) as a Chargé de Recherche (research scientist) in the Fresnel Institute of Marseille. Group leader at the Institute for Developmental Biology of Marseilles-Luminy (IBDM) and CNRS research director since 2009, his current research focuses on cell dynamics and mechanics in the context of tissue morphogenesis.

monika Ludanyi
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monika Ludanyi

Technical staff

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Sofia Yousfi

Trainee

Eunice hoyee Chan
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Eunice hoyee Chan

Researcher

Eunice joined the Lenne Lab in July 2012. She obtained her Ph.D. degree at the Max-Planck Institute in 2007. She becomes interested in epithelial biology during her postdoc work at London Research Institute. Currently, in IBDML, she is using advanced imaging and biophysical techniques to investigate the roles of Cadherins in shaping cone cell geometry during Drosophila retinal epithelial morphogenesis.

Claire Chardes
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Claire Chardes

Technical staff

Claire Chardès joined the team in 2009. Claire graduated in 2004 from the engineer school ENSPM (‘Ecole Nationale Supérieure de Physique de Marseille). Her project focuses on light sheet microscopy (SPIM and DSLM). She also participates in other projects in optics, image processing and image analysis.

Pruthvi Chavadimane Shivakumar
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Pruthvi Chavadimane Shivakumar

PhD student

Raphael Clement
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Raphael Clement

Researcher

Edith Laugier
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Edith Laugier

Technical staff

olivier Loison
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olivier Loison

Technical staff

Pierre Mangeol
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Pierre Mangeol

Researcher

Pierre Recouvreux
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Pierre Recouvreux

University lecturer

Pierre joined the lab in September 2013 as a University lecturer. He studied physics at the Ecole Normale Supérieure de Lyon (France) before focusing his research on the physics of biological systems. Pierre completed his PhD at the Institut Curie (Paris, France) working on the mechanical properties of single chromatin fibers using magnetic tweezers (under the supervision of J-L. Viovy). In 2010, he joined the group of Marileen Dogterom (AMOLF Insitute, Amsterdam) as a postdoctoral researcher. He worked on the microtubule-based establishment of polarization in fission yeast cells. In the group Pierre is now working on the physical aspects of neurulation in Caenorhabditis elegans embryos, in collaboration with the group of Vincent Bertrand at the IBDM.

Alumni

  • Olga Markova, Post-doctoral fellow, Institut Curie,Paris
  • Olivier Blanc, Research Engineer, Institut Jacques Monod, Paris
  • Jérémie Capoulade, Post-doctoral fellow, Leiden University, Netherlands
  • Emilien Etienne, Research Engineer, CNRS-Marseille
  • Matteo Rauzi, Post-doctoral fellow, EMBL Heidelberg, Maria Leptin’s lab
  • Pascale Vérant, Professeur ‘Classe préparatoires aux Grandes Ecoles’
  • Laure Wawrezinieck, Professeur ‘Classe préparatoires aux Grandes Ecoles’

Overview

Model organism
Biological process studied
  • Physical approaches to cell dynamics and tissue morphogenesis
  • Morphogenesis
  • Cell shapes
Technical approaches
  • Super-resolution Optical Microscopy
  • Sheet illumination microscopy
  • Optical Tweezers
  • Laser nanodissection
  • Fluorescence Correlation Spectroscopy
  • Physical modeling
  • Genetics
Medical applications
  • New approaches for biomedical imaging