Biomimetism of Cellular Movement

Cécile Sykes

Cécile Sykes Principal Investigator Tel:

Plastino_Sykes

Julie Plastino Principal Investigator Tel:

The ultimate goal of our work is to understand how cells change shape and move, with implications for understanding cancer invasion and metastasis.  We use biomimetic systems and simple cellular and animal models to study cell shape change under controlled conditions.  Using such approaches, we can dissect the physical and biochemical mechanisms governing cell shape change and movement.

 Figure 1: A liposome doublet is covered with actin filaments and myosin motors and reproduces tension build up in cells. Its change in shape (flattening of the angle between the two liposomes) allows for an estimation of the produced tension.

Figure 1: A liposome doublet is covered with actin filaments and myosin motors and reproduces tension build up in cells. Its change in shape (flattening of the angle between the two liposomes) allows for an estimation of the produced tension.

In the past we have successfully mimicked actin-based propulsion, where actin polymerization is reproduced in a controlled fashion on surfaces by attaching actin polymerization activators.  These surfaces include hard beads, soft beads and inner or outer leaflets of lipid bilayers of liposomes.  The objects are then incubated in cell extracts or in pure protein mixes and the actin structures that grow from the surfaces mimic the cellular actin cytoskeleton.  This set-up lends itself to quantitative measurements of the mechanism of cell cytoskeleton assembly and its mechanics. We are now developing systems with molecular motors and membranes that reproduce cell shape changes and cortical acto-myosin dynamics. For example the addition of myosin motors to the actin network next to a liposome membrane reproduces cell tension that can be quantified using liposome doublets (Figure 1).

In parallel with our work on reconstituted systems, we study similar acto-myosin structures in simple in vivo models, including cells in culture, mouse oocytes, Caenorhabditis elegans embryos and the anchor cell during basement membrane invasion in C. elegans (Figure 2).  In all cases, we examine how the biochemistry of actin assembly affects force generation and myosin activity, and how individual filament dynamics are integrated to produce overall cell shape changes during cell division, embryogenesis and development.

Figure 2 : Invasion de la cellule ancre pendant le développement de C. elegans. Vue de côté du ver en développement. La cellule ancre (inset, vert) force son passage au travers de la membrane basale (inset, rouge), en utilisant des protéases et la polymérisation de l'actine pour faire un trou qui devient la vulve du ver. Microscopie par DIC et épifluorescence.
Figure 2: Anchor cell invasion in C. elegans development. Side view of the developing worm. The anchor cell (inset, green) forces its way through a basement membrane (inset, red), employing proteases and actin polymerization to make a hole that becomes the worm vulva. DIC and epifluorescence microscopy.

 

Key publications

Year of publication 2015

Henri-François Renard, Mijo Simunovic, Joël Lemière, Emmanuel Boucrot, Maria Daniela Garcia-Castillo, Senthil Arumugam, Valérie Chambon, Christophe Lamaze, Christian Wunder, Anne K Kenworthy, Anne A Schmidt, Harvey T McMahon, Cécile Sykes, Patricia Bassereau, Ludger Johannes (2015 Jan 22)

Endophilin-A2 functions in membrane scission in clathrin-independent endocytosis.

Nature : 493-6 : DOI : 10.1038/nature14064

Year of publication 2014

Svitlana Havrylenko, Philippe Noguera, Majdouline Abou-Ghali, John Manzi, Fahima Faqir, Audrey Lamora, Christophe Guérin, Laurent Blanchoin, Julie Plastino (2014 Oct 29)

WAVE binds Ena/VASP for enhanced Arp2/3 complex-based actin assembly.

Molecular biology of the cell : 55-65 : DOI : 10.1091/mbc.E14-07-1200
Matthias Bussonnier, Kevin Carvalho, Joël Lemière, Jean-François Joanny, Cécile Sykes, Timo Betz (2014 Mar 28)

Mechanical detection of a long-range actin network emanating from a biomimetic cortex.

Biophysical journal : 854-62 : DOI : 10.1016/j.bpj.2014.07.008

Year of publication 2013

Kevin Carvalho, Feng-Ching Tsai, Feng C Tsai, Edouard Lees, Raphaël Voituriez, Gijsje H Koenderink, Cecile Sykes (2013 Sep 24)

Cell-sized liposomes reveal how actomyosin cortical tension drives shape change.

Proceedings of the National Academy of Sciences of the United States of America : 16456-61 : DOI : 10.1073/pnas.1221524110

Year of publication 2012

Clément Campillo, Pierre Sens, Darius Köster, Léa-Laetitia Pontani, Daniel Lévy, Patricia Bassereau, Pierre Nassoy, Cécile Sykes (2012 Sep 5)

Unexpected membrane dynamics unveiled by membrane nanotube extrusion.

Biophysical journal : 1248-56 : DOI : 10.1016/j.bpj.2013.01.051
Agnieszka Kawska, Kévin Carvalho, John Manzi, Rajaa Boujemaa-Paterski, Laurent Blanchoin, Jean-Louis Martiel, Cécile Sykes (2012 Aug 20)

How actin network dynamics control the onset of actin-based motility.

Proceedings of the National Academy of Sciences of the United States of America : 14440-5 : DOI : 10.1073/pnas.1117096109
All publications