Département PIV

Cell mechanics and mechanotransduction

Leader: E. Helfer, K. Sengupta


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).


Physical mechanisms of erythroid enucleation

Principal investigator:  E. Helfer

Postdoc: to be recruited

Collaborations: Zhangli Peng (University of Illinois at Chicago, USA), Peng Ji (Northwestern University, Chicago, USA)

Funding: ANR PRCI RedEnuc (2023-2026)

Erythropoiesis is the process of generating red blood cells. In mammals, red blood cells do not contain nuclei. Erythroblasts, the precursors of red blood cells, eliminate their nuclei when exiting the bone marow to reach blood microcirculation, where they will meture into red blood cells. The enucleation process is till not well understood, which hinders the in vitro production of red blood cells in culture, aimed for example for blood transfusion. We aim to elucidate the role of the external mechanical constraints applied on the erythroblast at exit from bone marrow, and that of internal forces generated by mechanosensitive processes, on expulsion and detachment of the nucleus. To do so, we are developing a microlfuidic device that will mimic the crowded environment of the bone marrow and allow us to observe the enucleation steps. We collaborate with a computer scientist who is a specialst of red blood cells under flow and a clinican biologist who is a specialit of erythropoiesis.


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






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


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

First-Principle Coarse-Graining Framework for Scale-Free Bell-Like Association and Dissociation Rates in Thermal and Active Systems

Josip Augustin Janeš, Cornelia Monzel, Daniel Schmidt, Rudolf Merkel, Udo Seifert, Kheya Sengupta, Ana-Sunčana Smith

Physical Review X 12:031030 (2022)10.1103/PhysRevX.12.031030

Physics of Organelle Membrane Bridging via Cytosolic Tethers is Distinct From Cell Adhesion

Mohammad Arif Kamal, Josip Augustin Janeš, Long Li, Franck Thibaudau, Ana-Sunčana Smith, Kheya Sengupta

Frontiers in Physics 9:1-12 (2022)10.3389/fphy.2021.750539

May the force be with your (immune) cells: an introduction to traction force microscopy in Immunology

Farah Mustapha, Kheya Sengupta, Pierre-Henri Puech

Frontiers in Physics 13:898558 (2022)10.3389/fimmu.2022.898558

Affinity driven ion exchange EG-OFET sensor for high selectivity and low limit of detection of Cesium in seawater

Tin Phan Nguy, Volkan Kilinc, Ryoma Hayakawa, Catherine Henry-De-Villeneuve, Jean-Manuel Raimundo, Yutaka Wakayama, Anne Charrier

Sensors and Actuators B: Chemical 351:130956 (2022)10.1016/j.snb.2021.130956

A Rare Mutation in LMNB2 Associated with Lipodystrophy Drives Premature Cell Senescence

Alice-Anaïs Varlet, Camille Desgrouas, Cécile Jebane, Nathalie Bonello-Palot, Patrice Bourgeois, Nicolas Levy, Emmanuèle Helfer, Noémie Dubois, René Valero, Catherine Badens, Sophie Beliard

Cells 11:50 (2022)10.3390/cells11010050


In situ plant materials hyperspectral imaging by multimodal scattering near-field optical microscopy

Anne Charrier, Aubin C Normand, Ali Passian, Philip Schaefer, Aude L. L. Lereu

Communications Materials 2:59 (2021)10.1038/s43246-021-00166-7

Biomechanics as driver of aggregation of tethers in adherent membranes

Long Li, Mohammad Arif Kamal, Bernd Henning Stumpf, Franck Thibaudau, Kheya Sengupta, Ana-Sunčana Smith

Soft Matter 17:10101-10107 (2021)10.1039/d1sm00921d

Ligand Nanocluster Array Enables Artificial-Intelligence-Based Detection of Hidden Features in T-Cell Architecture

Aya Nassereddine, Ahmed Abdelrahman, Emmanuelle Benard, F. Bedu, Igor Ozerov, Laurent Limozin, Kheya Sengupta

Nano Letters 21:5606-5613 (2021)10.1021/acs.nanolett.1c01073

Influence of force volume indentation parameters and processing method in wood cell walls nanomechanical studies

Aubin C Normand, Anne Charrier, Olivier Arnould, Aude L. Lereu

Scientific Reports 11:5739 (2021)10.1038/s41598-021-84994-0

Integrin-Functionalised Giant Unilamellar Vesicles via Gel-Assisted Formation: Good Practices and Pitfalls

Kheya Sengupta, Mariem Souissi, Julien Pernier, Olivier Rossier, Gregory Giannone, Christophe Le Clainche, Emmanuèle Helfer

International Journal of Molecular Sciences 22:6335 (2021)10.3390/ijms22126335

On the control of dispersion interactions between biological membranes and protein coated biointerfaces

Kheya Sengupta, Robert Blackwell, Arnaud Hemmerle, Andreas Baer, Matthias Späth, Wolfgang Peukert, Drew Parsons, Ana-Sunčana Smith

Journal of Colloid and Interface Science 598:464-473 (2021)10.1016/j.jcis.2021.02.078


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)

Nanomechanics and Raman Spectroscopy of in Situ Native Carbohydrate Storage Granules for Enhancing Starch Quality and Lignocellulosic Biomass Production

Rubye Farahi, Aude L. Lereu, Anne Charrier, Udaya C Kalluri, Brian H Davison, Ali Passian

ACS Omega 5:2594−2602 (2020)10.1021/acsomega.9b02849

Femtomolar detection of Cu2+ ions in solution using super-Nernstian FET-sensor with a lipid monolayer as top-gate dielectric

A. Kenaan, F. Brunel, J.-M. Raimundo, Anne Charrier

Sensors and Actuators B: Chemical 316:128147 (2020)10.1016/j.snb.2020.128147

Electrolyte-gated-organic field effect transistors functionalized by lipid monolayers with tunable pH sensitivity for sensor applications

Tin Phan Nguy, Ryoma Hayakawa, Volkan Kilinc, Matthieu Petit, Yemineni S L V Narayana, Masayoshi Higuchi, Jean-Manuel Raimundo, Anne Charrier, Yutaka Wakayama

Applied Physics Express 13:011005 (2020)10.7567/1882-0786/ab5322

Molecular and Mechanobiological Pathways Related to the Physiopathology of FPLD2

Alice-Anaïs Varlet, Emmanuèle Helfer, Catherine Badens

Cells 9:1947 (2020)10.3390/cells9091947


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

Novel and Innovative Interface as Potential Active Layer in Chem-FET Sensor Devices for the Specific Sensing of Cs+

Volkan Kilinc, Catherine Henry-De-Villeneuve, Tin Phan Nguy, Yutaka Wakayama, Anne M Charrier, Jean-Manuel Raimundo

ACS Applied Materials & Interfaces 11:47635-47641 (2019)10.1021/acsami.9b18188

Stable operation of water-gated organic field-effect transistor depending on channel flatness, electrode metals and surface treatment

Tin Phan Nguy, Ryoma Hayakawa, Volkan Kilinc, Matthieu Petit, Jean-Manuel Raimundo, Anne Charrier, Yutaka Wakayama

Japanese Journal of Applied Physics 58:SDDH02 (2019)10.7567/1347-4065/ab09d2

Biphasic mechanosensitivity of T cell receptor-mediated spreading of lymphocytes

Astrid Wahl, Céline Dinet, Pierre Dillard, Aya Nassereddine, Pierre-Henri Puech, Laurent Limozin, Kheya Sengupta

Proceedings of the National Academy of Sciences of the United States of America 116:5908-5913 (2019)10.1073/pnas.1811516116


T Cells on Engineered Substrates: The Impact of TCR Clustering Is Enhanced by LFA-1 Engagement

Emmanuelle Benard, Jacques Nunès, Laurent Limozin, Kheya Sengupta

Frontiers in Immunology 9 (2018)10.3389/fimmu.2018.02085

Nanometrology of Biomass for Bioenergy: The Role of Atomic Force Microscopy and Spectroscopy in Plant Cell Characterization

Anne Charrier, Aude L. Lereu, Rubye Farahi, Brian Davison, Ali Passian

Frontiers in Energy Research 6:11 (2018)10.3389/fenrg.2018.00011

Lamellipod Reconstruction by Three-Dimensional Reflection Interference Contrast Nanoscopy (3D-RICN)

Marie-Julie Dejardin, Arnaud Hemmerle, Anais Sadoun, Yannick Y. Hamon, Puech Pierre-Henri, Kheya Sengupta, Laurent Limozin

Nano Letters 18:6544-6550 (2018)10.1021/acs.nanolett.8b03134

Ultra-thin supported lipid monolayer with unprecedented mechanical and dielectric properties

Ahmad Kenaan, Racha El Zein, Volkan Kilinc, Sébastien Lamant, Jean-Manuel Raimundo, Anne Charrier

Advanced Functional Materials 1801024 (2018)10.1002/adfm.201801024

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