Systems Biology of Cell Polarity and Cell Division

Matthieu Piel

Matthieu Piel Team Leader Tel:

Our team studies cell polarization, a process which involves a reorganization of the cell cytoskeleton and movement of cellular organelles, usually triggered by external cues. We are particularly interested in cell polarity in the context of cell migration and cell division. We develop and use innovative tools based on nano and micro-fabrication techniques, to control and modulate the main physical and chemical parameters of the cell micro-environment. These tools are coupled with high quality quantitative microscopy, and used alongside molecular and cell biology techniques, to obtain a quantitative description of the cell behavior. As well as highlighting new basic concepts about cell polarity, our multidisciplinary approach leads to the development of novel tools with potential applications in biomedical research.

 

Here is a video that we produced for the ASCB about the life of a dendritic cell:

ASCB Celldance 2016 – Piel from ASCB on Vimeo.

Figure 1 : Our most recent innovation in cell micropatterning allows dynamic control of cell spreading (B), cell shape (D, E) and cell co-culture (C), using simple click-chemistry (A), see Van Dongen et al., Advanced Materials, 2013
Figure 1 : Our most recent innovation in cell micropatterning allows dynamic control of cell spreading (B), cell shape (D, E) and cell co-culture (C), using simple click-chemistry (A), see Van Dongen et al., Advanced Materials, 2013

We have demonstrated that micro-patterns of extra-cellular matrix molecules are able to determine the polarity and division axis of cultured cells. This discovery was patented and licensed to a start-up company (CYTOO, created in 2008) and we have kept developing this technology (see figure 1). In the past few years, we have developed other tools to control the cell micro-environment (micro-channels, confiners etc) and we have exploited them to understand how mechanical constrains affect cell division and migration.

The focus of our current research is how cells proliferate and migrate when space is limited. We want to understand how cells (immune cells and cancer cells) can produce efficient motion under confinement and squeeze through small holes. We also want to understand how physical constrains affect dividing cells.

Our current project on cell proliferation under external constrains has been awarded an ERC Consolidator grant in 2012.

Figure 2: (A) One of our recent discovery: external forces can orient cell division (see Fink et al. Nat. Cell Biol, 2011). (B) Rational of our current project on cells under confinement. (C) One of our confinement tools, here to study cell squeezing through a narrow gap (see Heuze et al. Meth. Mol Biol. 2010)
Figure 2: (A) One of our recent discovery: external forces can orient cell division (see Fink et al. Nat. Cell Biol, 2011). (B) Rational of our current project on cells under confinement. (C) One of our confinement tools, here to study cell squeezing through a narrow gap (see Heuze et al. Meth. Mol Biol. 2010)

M. Piel is author of more than 60 publications (H factor 26). He holds three patents, and is a co-founder of the CYTOO Company. He is teaching at the Center for Interdisciplinary Research in Institut Cochin. He also teaches cell biology and biophysics in several master courses in Paris. He is one of the founder of Institut Pierre-Gilles de Gennes for Microfluidics. He has been invited to over 30 international meetings and gave over 40 seminars in the last 5 years. He was awaded the Bronze medal of CNRS in 2012.

 

Subgroup: MOTILE (Mechanobiology Of Trans-Migration in Leukocytes) team headed by Pablo Vargas

Pablo Vargas
Since 2016, Pablo Vargas is part of the team as a permanent researcher (CR1 INSERM). His main interests are in understanding the mechanics behind the efficient migration of cells between distant organs. To do that, his group is using leukocytes specialized for migration in complex microenvironments.

 

  • Lucie BarbierLucie Barbier (PhD student): Mechanosensing via intracellular membranes.
  • pablo saezPablo Saez (postdoctoral researcher): Integration of physical and mechanical cues during chemotaxis.
  • mathieu deygasMathieu Deygas (postdoctoral researcher) : Integration of biochemical signals during migration in 3D microenvironments.

Key publications

Year of publication 2018

Clotilde Cadart, Sylvain Monnier, Jacopo Grilli, Pablo J Sáez, Nishit Srivastava, Rafaele Attia, Emmanuel Terriac, Buzz Baum, Marco Cosentino-Lagomarsino, Matthieu Piel (2018 Aug 18)

Size control in mammalian cells involves modulation of both growth rate and cell cycle duration.

Nature communications : 3275 : DOI : 10.1038/s41467-018-05393-0
Alculumbre SG, Saint-André V, Di Domizio J, Vargas P, Sirven P, Bost P, Maurin M, Maiuri P, Wery M, Roman MS, Savey L, Touzot M, Terrier B, Saadoun D, Conrad C, Gilliet M, Morillon A, Soumelis V (2018 Jan 1)

Diversification of human plasmacytoid predendritic cells in response to a single stimulus

Nature Immunology : 19(1) : 63-75 : DOI : 10.1038/s41590-017-0012-z

Year of publication 2017

Marine Bretou, Pablo J Sáez, Doriane Sanséau, Mathieu Maurin, Danielle Lankar, Melanie Chabaud, Carmine Spampanato, Odile Malbec, Lucie Barbier, Shmuel Muallem, Paolo Maiuri, Andrea Ballabio, Julie Helft, Matthieu Piel, Pablo Vargas, Ana-Maria Lennon-Duménil (2017 Oct 29)

Lysosome signaling controls the migration of dendritic cells.

Science immunology : DOI : eaak9573
Koceila Aizel, Andrew G Clark, Anthony Simon, Sara Geraldo, Anette Funfak, Pablo Vargas, Jérôme Bibette, Danijela Matic Vignjevic, Nicolas Bremond (2017 Oct 13)

A tuneable microfluidic system for long duration chemotaxis experiments in a 3D collagen matrix.

Lab on a chip : DOI : 10.1039/c7lc00649g
Pablo Vargas, Lucie Barbier, Pablo José Sáez, Matthieu Piel (2017 Jun 23)

Mechanisms for fast cell migration in complex environments.

Current opinion in cell biology : 72-78 : DOI : S0955-0674(17)30042-X

Year of publication 2016

M Raab, M Gentili, H de Belly, H R Thiam, P Vargas, A J Jimenez, F Lautenschlaeger, Raphaël Voituriez, A M Lennon-Duménil, N Manel, M Piel (2016 Apr 15)

ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death

Science (New York, N.Y.) : DOI : 10.1126/science.aad7611
All publications