# Research

## Active cellular systems

Active muticellular systems, such as cell monolayers or biological tissues, form perfect tilings of the space or plane, with organization that evolves in time because of cell activity, cell division (mitosis), cell death (apoptosis) or extrusion. In spite of the intrinsic stochasticity of these active local rearrangements, the integrity and shape of biological tissues are preserved, an essential feature to maintain their biological function.

In a study combining analytical and numerical investigations, we aim at understanding how structural fluctuations and defects affect — but also give insight to — the cohesion, the rigidity, and the integrity of an active multicellular system. As an illustration, we are currently characterizing the (in)stability and the fluctuations of the frontier between two active tissues.

## Mechanics of elastic beams

Various elastic systems can be understood as networks of interconnected struts which deform by a combination of bending, stretching, twisting and shearing mechanisms. Examples include paper sheets, polymer gels, protein networks and cytoskeletal structures , crystal atomic lattices, granular materials, foams, wood, bones... Moreover, the pairwise interaction potentials used in standard elastic percolation models can also be identified with the strain energy of elastic struts. Despite extensive research, the connection between the mechanical properties of such networks on a macroscopic level and the description of their structures on a microscopic level has not been completely elucidated yet.

Interestingly, under identical loading conditions, some structures appear to deform primarily through the local stretching of the struts, while in other structures the elastic energy is stored via local bending (twisting and shearing contributions are usually neglected). For instance, "foam-like" cellular architectures tend to be bending-dominated, while fibrous architectures exhibit a rich mechanical behavior: computational studies of the two-dimensional elastic deformation of a network of cross-linked fibers have shown a transition from a nonaffine, bending-dominated regime to an affine, stretch-dominated regime with increasing density of fibers. Recent experimental studies, have confirmed this transition.

We performed an analytical study of the macroscopic properties of elastic networks of beams. Our analysis provides a convenient set of geometrical criteria to identify the networks which deform exclusively by extension or compression of their members. Values of the effective elastic moduli of such networks are also derived. These results shed light on the relationship between microscopic geometry and macroscopic mechanics of elastic networks. In particular, they explain the difference in mechanical behavior of cellular and fiber networks.

## Transport networks

Finding the most efficient transport network is an issue arising in a wide variety of contexts. One can cite, among others, the water, natural gas and power supply of a city, telecommunication networks, rail and road traffic, and more recently the design of labs-on-chips or microfluidic devices. Moreover, this problem also appears in theoretical works intending to describe the architecture of the vascular systems of living organisms. Generally speaking, consider a set of sources and sinks embedded in a two- or three-dimensional space, their respective number and locations being fixed. The flow rates into the network from each source, and out of the network through each sink, are also given. The problem consists in interconnecting the sources and sinks via possible intermediate junctions, referred to as additional nodes, in the most efficient way. That is, to minimize a cost function of general form $\sum_{k} w_k f(i_k)$ , where the summation is over all the links that constitute the network. $w_k$ is the "weight" associated with the $k^{th}$ link, and is some function of the flow rate $i_k$ carried by this link. Minimization of the cost function can be done over different optimization parameters and with different constraints.

We have studied the structure of pipe networks that minimize the total dissipation rate $U=\sum_{k}r_k i_k^2$ is studied, where the weight $r_k$ is the "flow resistance" of pipe $k$, defined as: $r_k=\rho ~ l_k/ s_k^m$ , $\rho$ being some positive constant, $l_k$ and $s_k$ the length and cross-sectional area of each pipe respectively, and $m$ a positive constant characterizing the flow profile. For most flows encountered in physics, $m \geq 1$ . We have characterized the geometrical and topological features of such networks.

## Correlations between topological and geometrical disorders in soft cellular systems

Cellular materials are interesting both as disordered media with well-defined structural elements, and as models for more complex systems such as biological tissues. Among them, foams are ubiquitous in our daily lives and in many industries. Bubble monolayers are much easier to observe and to study. Such quasi two-dimensional foams are characterised by their number of bubbles, N, area distribution, p(A), and number-of-sides distribution, p(n). When the liquid fraction is very low (“dry” foams), their bubbles are polygonal, with shapes that are locally governed by Plateau’s laws. Each side is a thin liquid film with a uniform surface tension; its curvature is determined by the difference of pressure between the two bubbles it separates. Bubble size distribution and packing (or “topology”) are crucial in determining e.g. rheological properties or coarsening rate. When a foam is shuffled (either mechanically or thermally), N and p(A) remain fixed, but bubbles undergo “T1” neighbour changes, which induce a random exploration of the foam configurations.

In two-dimensional foams, we explore the relation between the distributions of bubble number-of-sides (topology) and bubble areas (geometry). We develop a statistical model which takes into account physical ingredients based on Plateau laws. The model predicts that the mean number of sides of a bubble with area A within a foam sample with moderate size dispersity is given by:

where ⟨.⟩ denotes the average over all bubbles in the foam. The model also relates the topological disorder Δn/⟨n⟩=√⟨n^2⟩−⟨n⟩^2/⟨n⟩ to the (known) moments of the size distribution:

Extensive data sets arising from experiments and simulations all collapse surprisingly well on a straight line, even at extremely high values of geometrical disorder. At the other extreme, when approaching the perfectly regular honeycomb pattern, we identify and quantitatively discuss a crystallisation mechanism whereby topological disorder vanishes.

## Order-disorder transition in 2d soft cellular systems

Under small strains, a foam behaves elastically, with stress proportional to strain and no bubble rearrangements. Above the yield strain, bubble rearrangements occur and the foam deforms plastically. We call T1 the elementary neighbor switching event. In a regular (hexagonal) foam, a T1 event corresponds to the creation of paired dislocations (where a dislocation itself is composed of one 5-sided and one 7-sided bubbles). When the applied shear strain increases, the number of dislocations keeps increasing, and the foam structure gets more and more disordered.

This behavior is reminiscent of that of a two-dimensional crystal submitted to an increasing temperature. This comparison suggests that strain acts as an effective temperature for the foam structure. To probe further this hypothesis, we studied numerically the order-disorder transition driven by an effective temperature in a soft cellular system. We highlighte the existence of an intermediate "hexatic" phase in which positional order vanishes but orientational order is preserved. However, we found that the transition does not follow the standard Kosterlitz, Thouless, Halperin, Nelson and Young (KTHNY) scenario observed in many two-dimensional solids, in which dislocations split into two separate disclinations as temperature keeps increasing, but instead follows a dislocation condensation scenario.

## Flows and contractile activity in Physarum Polycephalum

Throughout life, adequate adaptation and growth of vascular networks are essential for our well being. In many diseases, i.e. cancer, hypertension, macular degeneration, diabetic retinopathy, etc., vascular adaptation is impaired. Understanding how vascular networks form might help to develop better treatment strategies or maybe even ways to prevent these diseases. Vascular morphogenesis is partly determined by self organized actions of shear stresses generated by the circulating blood and mechanical stresses generated by the growing, deforming surrounding tissue. The core of this work is to study the role of mechanical self-organized processes in growing tissue for vascular morphogenesis and to identify the basic physical laws that shape the vascular networks.

We study experimentally the vascular morphogenesis and the synchronization of the contractile activity in P. Polycephalum.

## Dynamics and fluctuations of bilayer membranes

Biological membranes are lipid bilayers forming the envelopes of plasma membranes, nuclei, organelles, tubules and transport vesicles within a cell. They are versatile structures, both fluid and elastic, that can change shape or topology in order to accomplish the cell functions. From the dynamical point of view, membranes can be viewed as a system of four fluid phases in contact: a pair of two-dimensional (2D) lipid phases and two three-dimensional (3D) aqueous phases. These phases, separated but strongly coupled, exhibit nontrivial multiphase flow behaviors.

The dynamics of bilayer membranes containing transmembrane proteins at a high concentration are especially challenging because the proteins form a fifth phase that effectively interdigitates two components of the multiphase flow. This situation corresponds to the actual biological one, where macromolecular crowding effects are ubiquitous and which are known to make molecules in cells behave in radically different ways than in artificial lipid vesicles. Simple bilayer membranes already have a complex hydrodynamic behavior due to their soft out-of-plane elasticity. In the early studies of membrane hydrodynamics the bilayer structure of the membrane was neglected. While this is a good approximation for tensionless membranes at length-scales much larger than microns, experiments and theoretical studies have shown that taking the bilayer structure into account is essential at shorter length-scales. This is chiefly due to the importance of the dissipation due to the intermonolayer friction. The latter is caused by the relative motion of the lipid tails occurring when the two monolayers have different velocities. Clearly, in the case of membranes hosting integral proteins, an increase of the intermonolayer friction is expected.

We have studied the multiphase flow of an almost planar deformable bilayer membrane hosting diffusing transmembrane proteins of arbitrary shape. we have highlighted and quantified the increase in inter-monolayer friction due to the presence of proteins, as well as the anomalous character of the diffusive regime of proteins.

We also involved in the clarification of the different definitions of membrane tension. Using the formalism of statistical physics, we have shown that the amplitude of the thermal undulations of a membrane depends explicitly on its frame tension, conjugated to the area of the frame on which the membrane rests, and not on its intrinsic tension, conjugated to the real membrane area. This result contradicts the expression obtained by the classical treatment based on the Monge parametrisation, which is the expression used in the majority of publications on the subject. I have shown that it is mis-counting of the different membrane configurations that leads to an erroneous result with the classical treatment.