Cell mechanics and mechanotransduction

T cell mechanics

Principal investigators: K. SENGUPTA

PhD Student: Celine Dinet (2014-2018), Farah Mustafa (2018-2022)

Postdocs: Astrid Wahl (2016-2018), Fabio Manca (2020-2022)

Collaborations: P-H. Puech, Laurent Limozin (LAI, Marseille)

Funding: ERC (SYNINTER 2013-2018), AMU ED 352 PhD grant (Celine Dinet 2014-2017), ATER AMU (Celine Dinet 2018), DOC2AMU PhD grant (Farah Mustafa 2018-2022), CENTURI Post Doc (Fabio Manca 2020-2022).

It is now well established that living cells respond to the mechanics of their microenvironment, and that they exert forces to do so. We have shown that unlike tissue-forming cells, which respond monotonically to increasing environmental stiffness, T cells have a biphasic response when they use their special receptor - the T cell receptor (TCR) - to adhere. Based on observations of the early interaction of T cells with soft and rigid substrates, we show how the mechanics of molecular ligands are amplified at the cellular level. In addition, we measured the weak forces exerted by T cells on ultra-soft substrates at early times - experiments that lay the foundation for a better understanding of T cell mechanics.

Physics of cellular senescence

Principal investigator:  E. Helfer

PhD student: C. Jebane (2018-2022)

Collaborations: C. Badens (MMG, Marseille, France); J.-F. Rupprecht (CPT, Marseille, France)

Funding: AMIDEX MecaLam (2018-2022)

Cellular aging, named senescence, is a normal process during which cell functions progresseively degrade, until cell death. Senescence can also occur prematurely, for example in laminopathies, genetic diseases associated with mutations in proteins of the lamina, a key component of the nuclear envelope (NE). While the consequences of these diseases are known, the relationship between their severity, mutations and mechanical alterations at the cellular/nuclear level is still unknown. We focus on mechanical alterations specifically related to defects in lamin A/C, one of the components of the lamina. We use a microfluidic approach coupled to a classical rheological model to quantify the mechanical properties of prematurely senescent cells. We recently showed an increase in the effective viscosity of senescent cells, never observed before. This change does not depend solely on the nuclear mechanics, but it is largely dominated by the cell cytoskeleton, which is connected to the nucleus. Our results show that alterations in lamin A affect the nucleus, but also its links to the cytoskeleton.

Impact of cell mechanics and signalling crosstalk on cell differentiation.

Principal Investigator: E. Helfer

Postdoc: Jack Llewellyn

Collaborations: Rosanna Dono (IBDM, Marseille, France)

Funding: CENTURI (2022-2023)

We aim to understand how human-induced pluripotent stem cells (hiPSCs) respond to differentiation signals depending on their mechanical environment. We first study how they respond to biochemical signals when adhered on substrates of varying rigidity. We will then quanttify the forces they generate on the substrates using Traction Force Microscopy (TFM).

Towards the understanding of tension generation mechanisms in wood

Principal investigators: A. CHARRIER

PhD Student: Aubin Normand (defended)

Collaborations: A. Lereu (Institut Fresnel, Marseille), A. Passian (Oak Ridge National Laboratory, USA), O. Arnould (Laboratoire de Mécanique et Génie Civil, Montpellier), Pépinière expérimentale de l’Etat à Cadarache, NEASPEC GMBH (Allemagne)

Funding: IDEX AMU(2018-2022), PICS CNRS (2019-2022), PhD grant: Aubin Normand (2018-2022)

With 3000 billion trees, wood is one of the most widespread materials on Earth, it is also renewable and biodegradable, and it plays an omnipresent role in the maintenance and shaping of human societies. Its great diversity is expressed in a wide variety of physical and bio-chemical properties giving it different functionalities involved in our daily life, for example operating functions for building, paper or energy... Surprisingly, this diversity is obtained only from three polymers: cellulose, hemicellulose and lignin representing more than 95% of wood constituents. The diversity comes from the arrangement and proportions of these polymers. Trees have a hierarchical structure, i.e. their macroscopic properties and appearances come from their structures at the micro and nanometric scales. This leads to the question of the relationship between chemical distribution, structural organization and physical properties at the nanoscale. How will nanoscale variations influence the overall response of the tree? And conversely how can external action modify the molecular arrangement and associated properties?

A particularly interesting example is the ability of trees to straighten and align themselves with the direction of gravity, to control the angle of growth of branches, or to improve their resistance to wind, while optimizing the proportion of biomass allocated to these functions. Thus, trees have an active motor mechanism, analogous to muscles in animals, in the form of internal stresses generated during secondary (radial) tree growth. In this project, our objective is to provide insight into the mechanisms leading to the creation of these stresses by providing quantitative correlated data on the chemical distribution of the different wood constituents and on the mechanical properties at the cell wall scale.

See the movie: Expérimenter l’avenir : Le bois de tension, matériau renouvelable et biodégradable, Collection AMIDEX, https://www.youtube.com/watch?v=JLDRaEduz1U