Résumés:

 

 

 

Multiwave Imaging : A solution to image rheological properties of soft tissues.

Mathias Fink

(Institut Langevin, Ecole Supérieure de Physique et de Chimie Industrielles)

 

We describe a new concept for imaging soft solids. The idea is that very different waves -- one to provide contrast, another to provide spatial resolution -- can be productively combined to generate something akin to near-field imaging. We will focus specifically on imaging rheological properties of soft biological tissues. Here, the multi-wave approach relies on the simultaneous use of both sonic shear waves and ultrasonic compressional waves. The sonic shear wave has typically centimetric wavelengths and propagates at low velocity in tissues (between 1 and 10 m/s). They are progressively distorted by the viscoelastic inhomogeneities of encountered tissues. When coupled to an ultrafast ultrasound scanner (10.000 images per second), it allows for the follow up of the propagation of these waves with a sub millimetric resolution over a large zone of interest. From the spatio-temporal evolution of the displacement fields, inversion algorithms are used to recover the rheological properties with sub-millimetric resolution. These techniques are no more diffraction limited because, the near field of the shear waves is directly observed. Here, the shear wave gives the contrast (viscoelasticity) while the ultrasonic wave gives the spatial resolution. Various examples of in vivo images will presented in breast, liver, eyes, muscles, cardiac applications that show the interest of this quantitative imaging technique in diagnostic and therapy monitoring.

Cooperativity between integrin activation and mechanical stress leads to integrin clustering

 Bertrand Fourcade

(IJF, Grenoble)

 

 

Integrins are transmembrane receptors involved in crucial cellular  biological functions such as migration, adhesion and spreading. Upon the  modulation of integrin affinity towards their ligands by cytoplasmic  proteins (inside-out signaling) these receptors bind to their  extracellular ligands and cluster into nascent adhesions. This  clustering results in the increase in the mechanical linkage between the  cell and substratum, cytoskeleton rearrangements, and further outside-in  signaling. Based on  experimental observations of the distribution of  focal adhesions in cells attached to micro-patterned surfaces, we  introduce a physical model relying on experimental numerical constants  determined in the literature. In this model, allosteric integrin  activation  works in synergy with the stress build by adhesion and the  membrane rigidity to allow the clustering to nascent adhesions  independently of actin but dependent on the integrin diffusion onto  adhesive surfaces. The initial clustering could provide a template to  the mature adhesive structures. Predictions of our model for the  organization of focal adhesions are discussed in comparison with  experiments using adhesive protein microarrays.

Bacterial strategies for chemotactical responses

Antonio Celani

(Institut Pasteur, Paris)

 

Regular environmental conditions allow for the evolution of specifically adapted responses, whereas complex environments usually lead to conflicting requirements upon the organism’s response. A relevant instance of these issues is bacterial chemotaxis, where the evolutionary and functional reasons for the experimentally observed response to chemoattractants remain a riddle. Sensing and motility requirements are in fact optimized by different responses, which strongly depend on the chemoattractant environmental profiles. It is not clear then how those conflicting requirements quantitatively combine and compromise in shaping the chemotaxis response. Here we show that experimental bacterial response corresponds to the maximin strategy that ensures the highest minimum uptake of chemoattractants for any profile of concentration. We show that the maximin response is the unique one that always outcompetes motile but nonchemotactic bacteria. The maximin strategy is adapted to the variable environments experienced by bacteria, and we explicitly show its emergence in simulations of bacterial populations in a chemostat.

Le mouvement de croissances des feuilles révèlent-ils leur mécanique?

Stéphane Douady

 (MSC, Paris 7)

 

Les feuilles en se développant présentent de nombreux mouvements. Pour commencer, certaines se plient lors de leur croissance dans le bourgeon (ce qui influence directement leur forme). Ensuite en se dépliant, les feuilles présentent des mouvements exagérés, avant de devenir finalement planes. Enfin même lors de ces mouvements, elles sont constamment en train d'osciller, de manière rapide (3h). Quel est l'intérêt de ces mouvements? Que peut-on en déduire sur la mécanique des tissus des feuilles en croissance?

Colloque

 

Physique et Mécanique des Systèmes Biologiques

 

Icosahedral viruses : physical principles of capsid structure classification, self-assembly and maturation

V.L. Lorman, (avec S.B. Rochal)

(Département de Physique Théorique, Laboratoire Charles Coulomb, UMR 5221 CNRS-Université Montpellier II)

Viruses are biological systems with high level of spatial organization well suited to modern  physical methods of study. Viral genome is protected by a solid protein shell (capsid) made of many copies of identical subunits (one or few proteins). Recent physical, mechanical and biochemical data rise a whole number of questions concerning unconventional positional order of subunits in the shell, thermodynamics and physical mechanisms of the self-assembly, shape and mechanical stability of the shell. In the present work we develop the theory which explains and classifies the capsid structures for viruses with spherical topology and icosahedral symmetry. The theory  developed is based on the statistical physics principles and on the symmetry properties of coat proteins. We develop an explicit method which predicts the positions of centers of mass for the proteins constituting viral capsid, including the capsids of unusual viruses discovered quite recently. The peculiarities of the assembly thermodynamics are also discussed. We show the relation between the protein density distributions obtained and the infectivity properties for several human viruses. To illustrate the notions of the theory and the results obtained we focus on the Dengue virus capsid, its herringbone-like structure, its infectivity and pH-driven capsid reconstruction during the maturation process in the cellular pathway. Universal characteristics of polymorph mutant viruses and virus-like particles are introduced.

Active force generation in biological tissues

Davide Ambrosi

(MOX laboratory, Politecnico di Milano)

 

The application of the methods of classical continuum mechanics to living  tissues, namely the cardiac muscle, faces a peculiar behavior: the ability of  a living body to deform by its own action, even without external loads. The  mathematical representation of this fact is usually approached in the engineering literature by the introduction of an additive surface force  contribution, the "active stress tensor", to be included in the force balance  equation. An alternative approach, recently proposed, models the activity of  muscles as an "active deformation" that enters in the equations thanks a multiplicative decomposition of the gradient of deformation, reminiscent of  classical approaches in plasticity. In my talk I will point out some  mathematical aspects and open questions that pertain both approaches.

Cellular mechanics and cell interactions in cancer

Claude Verdier

(IJF Grenoble)

 

The processes by which cancer cells interact with the vessel walls (endothelial cells) and extravasate through the endothelium lining are discussed. Such processes are mediated by cellular adhesion as well as cell mechanical properties. More precisely, different methods can be used to control the mechanical forces using flow chambers or AFM.

Complementary experiments using TFM (Traction Force Microscopy) allow the investigation of cell migration and cell interactions.

Branching patterns and cell colonies

Benoit Perthame

(Laboratoire J.-L. Lions, UPMC, INRIA-Rocquencourt and Institut Universitaire de France)

 

The question of understanding the formation of bacterial colonies and their invasion strategy is still under investigation. Several PDE models are known to undergo branching instability. Among those, one of the most famous, inspired by the Gray-Scoot model of chemical reaction, creates dentritic growth; it describes the growth of a cell population under the effect of a nutrient which is locally depleted.

However, a conservative parabolic model that includes the 'quorum sensing' limitation has been proposed by Dolak and Schmeiser. The swarmer cells are modeled by a Fokker-Planck type equation a la Keller-Segel. We show that coupled with two fields describing short range attraction and long range repulsion, the model can also undergo branching instabilities. Several reduced models explain stability and instability of plateau type traveling wave solutions.

This lecture is based on collaborations with F. Cerreti, Ch.  Schmeiser, M. Tang and N. Vauchelet

Contour instability in early melanoma growth

Clément Chatelain, (avec M. Ben Amar, P. Ciarletta)

(LPS, Ecole Normale Supérieure)

 

Early detection of cutaneous melanoma is crucial for a successful treatment. Current diagnostic methods in clinical dermatology are based on some morphological characteristics of the pigmented skin lesions and result mostly of statistical studies. Our goal is to analyze how shape instabilities can occur during the radial growth phase of melanoma to improve the interpretation of the observed in vivo patterns. A multiphase mixture framework is chosen to model the melanoma early growth accounting for the biomechanical characteristics of its micro-environment. We present a new analytical method for studying the stability properties of the resulting coupled PDE. In particular, we identify a control parameter governing a bifurcation during radial growth with loss of circular symmetry and we connect cells phenotype and micro-environment properties to tumor shape evolution. While applied here to cutaneous melanoma, our analytical method is very general and other relevant applications can be envisaged for solving problems of tissue growth and remodeling.

 

Reflections on the problem of the longitudinal growth of long bones in mammals

Gérard Maugin

(Institut d’Alembert, UPMC)

 

The slow lengthening of long bones in mammals via the evolution of the so-called growth plate is an interesting problem of mechanobiology. First analogies and differences between the evolution of the growth plate and the progress of phase-transformation fronts are noted. Second, on account of biophysical data several modellings of the growth plate itself and its progress are considered. Finally, the special modelling that views the growth plate as a zone of gradient variation of its structural properties but in very slow time evolution is considered. The possibility to exploit nonlinear signals (bell shapes, kinks) in the nonlinear elasticity of the considered tissues superimposed on this quasi-static evolution, is then envisaged delivering various signatures for these signals, which are characteristic of the considered growth plate structure.

Works in co-operation with A.B. Freidin and A.V. Porubov (St Petersburg) and M. Rousseau (Paris).

Theory for the DNA supercoiling transition in extension-rotation  experiments.

Sébastien Neukirch (avec J. Marko)

(Institut d’alembert UPMC)

 

Extension jumps were recently observed in single-molecule experiments where a DNA molecule (few kbp long) is held under tension while its  ends are slowly rotated. For low rotation the molecule is believed to  adopt (disordered) straight configurations and when a rotation threshold is reached the molecule jumps into a supercoiled phase:  plectonemes arise. The transition is not continuous: the end-to-end  extension of the molecule experiences an abrupt decrease.

We develop a theory where we compare the free-energies of the straight  and supercoiled states. Care is taken with the energy of the  supercoiled state where bending and twist energies for the plectonemes tip and the region joining the plectonemes and the ends of the molecules are included.

We find that the free energies of the straight and supercoiled states cross for a value n* of the imposed rotation. The extension jump is then given by the difference between the extension of the two states. 

On the harmonization of growth

Arezki Boudaoud

(ENS Lyon)

 

Inhomogeneous growth is essential in morphogenesis. However, a given tissue is often found to grow homogeneously although each cell could have its own growth rate. How can cells in a tissue achieve a homogeneous growth rate?

Using a combination of experiments on the model plant Arabidopsis and cell-based simulations, we propose a role for osmotic pressure and for the cytoskeleton in the harmonization of growth.

Fluctuations and instabilities of epithelial tissues

Jacques Prost

(ESPCI Paris)

 

Making use of the continuum description introduced in the preceding lecture of J.F. Joanny, I will discuss first how the stochasticity of cell division and apoptosis can influence interfacial behavior in a simple case. I will further discuss the stability of thick epithelial tissues and also the steady state of monolayer epithelia. A description keeping track of the interstitial fluid will also be discussed. It allows us to make a clear distinction between the stress acting on the cells and the interstitial fluid pressure. Size limitations of tissues due to gravity will also be discussed.

Collective migration of epithelial cells

Pascal Silberzan (avec M. Reffay, L. Petitjean, O. Cochet, A. Buguin)

(Institut Curie, Paris)

 

When free surface is made available to a confluent epithelium of strongly epithelial cells such as MDCK cells, they collectively migrate to cover the newly available surface while maintaining strong adhesions between them. By using correlations-based imaging techniques, we observe that this collective motility involves long-range coordinated displacements of large groups of cells well within the monolayer. This observation contradicts the commonly accepted view in which only the border cells are affected.

In a second stage, the edges of these wounds roughen drastically and exhibit a strong directional fingering led by a “leader cell” of different phenotype. Interestingly, similarly looking structures are found in a large number of different situations in morphogenesis or local invasion from tumors. We fully map several quantities in these fingers (velocity, orientation of the cells, orientation of their division axis, position of the MTOC relatively to their nucleus). Although all these directions align with the fingers, they are described by different order parameters and kinetics. Complementary laser photo-ablation experiments help to clarify the mechanical interplay between the leader and. the other cells of the fingers.

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