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We discuss the growth of biological tissues and the role of mechanical stresses on tissue growth. The guiding idea is to consider a tissue as a material and to make a continuum mechanics description by building the equivalent of a constitutive equation of the tissue relating the stress in the tissue to a local deformation (strain) or a velocity gradient. However, we need to take into account specific features of tissues. A tissue is a living material, which consumes energy and therefore it cannot be described by equilibrium thermodynamics. A tissue grows because cells divide and it shrinks because cells die. The number of cells in a tissue is therefore not constant. While we lay out this program, we have in mind two types of tissues for which cell division and cell death play an important role: cancerous tissues and animal tissues during early development.

The volume of adhered cells has been shown experimentally to decrease during spreading. This effect can be understood from the pump-leak model, which we have extended to include mechano-sensitive ion transporters. We identify a novel effect that has important consequences on cellular volume loss; cells that are swollen due to a modulation of ion transport rates are more susceptible to volume loss in response to a tension increase. This effect explains in a plausible manner the discrepancies between three recent, independent experiments on adhered cells, between which both the magnitude of the volume change and its dynamics varied substantially. We suggest that starved and synchronized cells in two of the experiments were in a swollen state and, consequently, exhibited a large volume loss at steady state. Non-swollen cells, for which there is a very small steady-state volume decrease, are still predicted to transiently lose volume during spreading due to a relaxing viscoelastic tension that is large compared with the steady-state tension. We elucidate the roles of cell swelling and surface tension in cellular volume regulation and discuss their possible microscopic origins.

Enseignement Cours – Physique des tissus biologiques Introduction Après un cours sur la matière active en 2019, les deux cours de 2020 et 2021 seront consacrés à la physique des tissus qui peuvent être considérés comme des exemples de matière active. Les cours mettent en avant le caractère actif des tissus, mais ils essaient de montrer aussi ce qu’une approche de physicien peut apporter à la biologie des tissus en discutant essentiellement deux types de tissus : les tissus cancéreux et les ti...

A fait l'objet d'un communiqué de presse CNRS - Institut Curie, le 9 août 2022:https://www.cnrs.fr/fr/auto-assemblage-moleculaire-reproduisant-le-mouvement-ondulatoire-des-flagelles-responsables-de-la; International audience; Wave-like beating of eukaryotic cilia and flagella—threadlike protrusions found in many cells and microorganisms—is a classic example of spontaneous mechanical oscillations in biology. This type of self-organized active matter raises the question of the coordination mechanism between molecular motor activity and cytoskeletal filament bending. Here we show that in the presence of myosin motors, polymerizing actin filaments self-assemble into polar bundles that exhibit wave-like beating. Importantly, filament beating is associated with myosin density waves initiated at twice the frequency of the actin-bending waves. A theoretical description based on curvature control of motor binding to the filaments and of motor activity explains our observations in a regime of high internal friction. Overall, our results indicate that the binding of myosin to actin depends on the actin bundle shape, providing a feedback mechanism between the myosin activity and filament deformations for the self-organization of large motor filament assemblies.

The progress of food in the gastrointestinal (GI) tract is driven by a peristaltic motion generated by the muscle belt surrounding the GI tract. In turn, the response of the intestinal epithelial cells to the peristaltic stresses affects the dynamics of the epithelial structure. In this work, we study the effect of cyclic stretching (0.125 Hz, 10% strain) on the spatial organization of the intestinal epithelium using intestinal cells deposited on a flat elastomeric substrate to mimic the peristaltic motion in vitro. A confluent monolayer of Caco-2 cells is grown on a PDMS chip to probe the morphological and orientational response of the tissue to cyclic stretching. The PDMS chips are either covalently or non-covalently coated with laminin to recapitulate the basement membrane. We observe a significant orientational response where the cells rearrange their long axes perpendicular to the stretching direction for both coating conditions. The experiment is modeled by a vertex model where the cells store elastic energy with varying strain and effectively have a rotational diffusive motion through rearrangements of their shapes. The model also predicts a transition between the perpendicular orientation and orientation at an oblique angle determined by the level of the cell elastic anisotropy. It provides a general framework to study cell response and relaxation dynamics under cyclic stretching across different cell types. We also discuss potential relevance of peristalsis in determining planar cell polarity in 3D architectures.

Simple hydrostatic skeletons such as the Hydra’s consist of two stacked layers of cells perpendicularly oriented. Although this crisscross architecture can be recapitulated in vitro, little is known on the formation of such multilayers starting from a monolayer. In the present article, we show that bilayering of myoblasts results from the organization and activity of the cells originally in the monolayer which can be described as a contractile active nematic. As expected, most of the +1/2 topological defects that are associated with this nematic order self-propel. However, a subpopulation of these defects remains immobile. Perpendicular bilayering occurs exclusively at these motionless defects. Indeed, cells located at the head of these defects converge toward the (immobile) core and accumulate there until they start migrating on top of the tail of the first layer while the tail cells migrate in the opposite direction under the head cells. Since the cells keep their initial orientations, the two stacked layers end up perpendicularly oriented. This concerted process leading to a bilayer is dependent on the apical secretion of Extra Cellular Matrix (ECM) by the cells. Indeed, we evidence the presence of ECM between the cell layers and at the apical surface of the topmost layer. ECM molecules are oriented in the direction of the cells that produce them, which may guide the migration of the subsequent cell layers on their apical side.Significance StatementHydrostatic skeletons such as that of the Hydra consist of two stacked layers of cells perpendicularly oriented whose coordinated contraction allows for complex movements. Such crisscross organization is also observed with myoblasts in culture. Confluent monolayers organize in well-aligned domains between which topological defects position themselves. Although these singularities are generally self-propelled, a fraction of them remains motionless. Perpendicular bilayering occurs exclusively at these particular pinned defects. Cells first accumulate at the head of the defects until they split in two perpendicular layers migrating in an antiparallel way on top of each other. Such a concerted process is highly dependent on the precise organization of the cell-secreted Extra Cellular Matrix (ECM).

Evidence suggests that the transport rate of a passive particle at long timescales is enhanced due to interactions with the surrounding active ones in a size- and composition-dependent manner. Using a system of particles with different temperatures, we probe these effects in dilute solutions and derive long-time friction and self-diffusion coefficients as functions of volume fractions, sizes and temperatures of particles in $d=2$ and 3 dimensions. Thus, we model excluded-volume interactions for nonequilibrium systems but also extend the scope to short-range soft potentials and compare our results to Brownian-dynamics simulations. Remarkably, we show that both viscosity and energy flux display a nonlinear dependence on size. The simplicity of our formalism allows to discover various interesting scenarios that can be relevant for biological systems and active colloids., Comment: Published version, main text and supplemental material

Mechanics has been a central focus of physical biology in the past decade. In comparison, the osmotic and electric properties of cells are less understood. Here we show that a parameter central to both the physics and the physiology of the cell, its volume, depends on a mechano-osmotic coupling. We found that cells change their volume depending on the rate at which they change shape, when they spread, migrate or are externally deformed. Cells undergo slow deformation at constant volume, while fast deformation leads to volume loss. We propose a mechano-sensitive pump and leak model to explain this phenomenon. Our model and experiments suggest that volume modulation depends on the state of the actin cortex and the coupling of ion fluxes to membrane tension. This mechano-osmotic coupling defines a membrane tension homeostasis module constantly at work in cells, causing volume fluctuations associated with fast cell shape changes, with potential consequences on cellular physiology.

Despite the absence of a membrane-enclosed nucleus, the bacterial DNA is typically condensed into a compact body - the nucleoid. This compaction influences the localization and dynamics of many cellular processes including transcription, translation, and cell division. Here, we develop a model that takes into account steric interactions among the components of the Escherichia coli transcriptional-translational machinery (TTM) and out-of-equilibrium effects of mRNA transcription, translation, and degradation, in order to explain many observed features of the nucleoid. We show that steric effects, due to the different molecular shapes of the TTM components, are sufficient to drive equilibrium phase separation of the DNA, explaining the formation and size of the nucleoid. In addition, we show that the observed positioning of the nucleoid at midcell is due to the out-of-equilibrium process of messenger RNA (mRNA) synthesis and degradation: mRNAs apply a pressure on both sides of the nucleoid, localizing it to midcell. We demonstrate that, as the cell grows, the production of these mRNAs is responsible for the nucleoid splitting into two lobes, and for their well-known positioning to 1/4 and 3/4 positions on the long cell axis. Finally, our model quantitatively accounts for the observed expansion of the nucleoid when the pool of cytoplasmic mRNAs is depleted. Overall, our study suggests that steric interactions and out-of-equilibrium effects of the TTM are key drivers of the internal spatial organization of bacterial cells., 21 pages, 11 figures

International audience; Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions. To perceive mechanical perturbations of different types and magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results of selective osmotic compressions of CT26 mouse cells within multicellular aggregates and global aggregate compressions, we show that global compressions have a strong impact on the aggregates growth and internal cell motility, while selective compressions of same magnitude have almost no effect. Both compressions alter the volume of individual cells in the same way over a shor-timescale, but, by draining the water out of the extracellular matrix, the global one imposes a residual compressive mechanical stress on the cells over a long-timescale, while the selective one does not. We conclude that the extracellular matrix is as a sensor that mechanically regulates cell proliferation and migration in a 3D environment.

Active fluids exhibit spontaneous flows with complex spatiotemporal structure, which have been observed in bacterial suspensions, sperm cells, cytoskeletal suspensions, self-propelled colloids, and cell tissues. Despite occurring in the absence of inertia, chaotic active flows are reminiscent of inertial turbulence, and hence they are known as active turbulence. Here, we survey the field, providing a unified perspective over different classes of active turbulence. To this end, we divide our review in sections for systems with either polar or nematic order, and with or without momentum conservation (wet/dry). Comparing to inertial turbulence, we highlight the emergence of power-law scaling with either universal or non-universal exponents. We also contrast scenarios for the transition from steady to chaotic flows, and we discuss the absence of energy cascades. We link this feature to both the existence of intrinsic length scales and the self-organized nature of energy injection in active turbulence, which are fundamental differences with inertial turbulence. We close by outlining the emerging picture, remaining challenges, and future directions., Comment: Review for Annu. Rev. Condens. Matter Phys

Polyampholytes (PAs) are polymers carrying electrical charges of both signs along their backbone. We consider synthetic PAs with a quenched random charge sequence. At low to moderate salt concentrations, PAs typically adopt pearl-necklace structures with collapsed globules linked by open strands. We study the structure of a PA as a function of its net charge by means of coarse-grained molecular dynamics simulations and analytical theory. It is shown theoretically and evidenced by simulations that the free energy drives quenched random PAs toward states with (very) polydisperse pearls. The translocation of a (partially) globular PA, driven by an electric field through a narrow pore, usually starts from a chain end in a tailed configuration. In our simulations, about half of all the observed PA configurations are tailed. The vast majority of the sequences visits tailed configurations long enough to initiate translocation like for open PAs. A detailed description of the tail size distribution and tail structure is obtained, and the survival statistics of tails is explored. The consequences of the pearl-necklace structures, observed in the simulations, for the translocation are discussed. Translocation itself is not simulated in this contribution.

We present a theory of active, permeating, polar gels, based on a two-fluid model. An active relative force between the gel components creates a steady-state current. We analyze its stability, while considering two polar coupling terms to the relative current: a permeation-deformation term, which describes network deformation by the solvent flow, and a permeation-alignment term, which describes the alignment of the polarization field by the network deformation and flow. Novel instability mechanisms emerge at finite wave vectors, suggesting the formation of periodic domains and mesophases. Our results can be used to determine the physical conditions required for various types of multicellular migration across tissues., Comment: 16 pages, 2 figures (Supplemental Material included)

This review presents the different physical descriptions of cell assemblies. After a short presentation of discrete models, very popular in studies of epithelial tissues, we focus more on multi-cellular spheroids containing a variety of components. In particular, we highlight both an approach based on the Smoluchowski theory of aggregation that does not consider the spatial structure of the aggregates and a continuous model for cell mixtures based on the Onsager formalism combined with the Rayleigh principle for the dynamics of dissipative systems. We show how the first approach allows to obtain the physical constants of the cells by comparison with experimental aggregates comprising a single cancerous cell line, while the second one determines the fate of interacting and proliferating cell mixing as a function of the access to nutrients. For both models, the formalism is deeply revisited to be adapted to the specificity and diversity of biological multi-component tissues. Finite element numerical simulations are shown to illustrate the potential of these physical studies.

Active fluids exhibit complex turbulentlike flows at low Reynolds number. Recent work predicted that 2D active nematic turbulence follows scaling laws with universal exponents. However, experimentally testing these predictions is conditioned by the coupling to the 3D environment. Here, we measure the spectrum of the kinetic energy E(q) in an active nematic film in contact with a passive oil layer. At small and intermediate scales, we find the scaling regimes E(q)∼q^{-4} and E(q)∼q^{-1}, respectively, in agreement with the theoretical prediction for 2D active nematics. At large scales, however, we find a new scaling E(q)∼q, which emerges when the dissipation is dominated by the 3D oil layer. In addition, we derive an explicit expression for the spectrum that spans all length scales, thus explaining and connecting the different scaling regimes. This allows us to fit the data and extract the length scale that controls the crossover to the new large-scale regime, which we tune by varying the oil viscosity. Overall, our work experimentally demonstrates the emergence of scaling laws with universal exponents in active turbulence, and it establishes how the spectrum is affected by external dissipation.

How much fluid adheres to an object pulled out from a liquid reservoir? We re-examine this dip-coating problem for yield-stress fluids. We propose a complete description that links the yield-stress fluid case with the Newtonian case. For extreme cases, asymptotic scaling laws are provided.

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions. To perceive mechanical perturbations of different types and magnitudes, tissues need appropriate detectors, with a compliance that matches the perturbation amplitude. By comparing results of selective osmotic compressions of cells within multicellular aggregates with small osmolites and global aggregate compressions with big osmolites, we show that global compressions have a strong impact on the aggregates growth and internal cell motility, while selective compressions of same magnitude have almost no effect. Both compressions alter the volume of individual cells in the same way but, by draining the water out of the extracellular matrix, the global one imposes a residual compressive mechanical stress on the cells while the selective one does not. We conclude that, in aggregates, the extracellular matrix is as a sensor which mechanically regulates cell proliferation and migration in a 3D environment.

International audience; We study the spreading of a Newtonian fluid by a deformable blade, a common industrial problem, characteristic of elasto-hydrodynamic situations. Here, we consider the case of a finite reservoir of liquid, emptying as the liquid is spread. We evidence the role of a central variable: the wetting length lw, which sets a boundary between the wet and dry parts of the blade. We show that the deposited film thickness e depends quadratically with lw. We study this problem experimentally and numerically by integration of the elasto-hydrodynamic equations, and finally propose a scaling law model to explain how lw influences the spreading dynamics.

The vertex model is widely used to describe the dynamics of epithelial tissues, because of its simplicity and versatility and the direct inclusion of biophysical parameters. Here, it is shown that quite generally, when cells modify their equilibrium perimeter due to their activity, or the tissue is subject to external stresses, the tissue becomes unstable with deformations that couple pure-shear or deviatoric modes, with rotation and expansion modes. For short times, these instabilities deform cells increasing their ellipticity while, at longer times, cells become non-convex, indicating that the vertex model ceases to be a valid description for tissues under these conditions. The agreement between the analytic calculations performed for a regular hexagonal tissue and the simulations of disordered tissues is excellent due to the homogenization of the tissue at long wavelengths.

The regulation of actin dynamics is essential for various cellular processes. Former evidence suggests a correlation between the function of non-conventional myosin motors and actin dynamics. Here we investigate the contribution of myosin 1b to actin dynamics using sliding motility assays. We observe that sliding on myosin 1b immobilized or bound to a fluid bilayer enhances actin depolymerization at the barbed end, while sliding on myosin II, although 5 times faster, has no effect. This work reveals a non-conventional myosin motor as another type of depolymerase and points to its singular interactions with the actin barbed end., Former evidence suggests a correlation between the function of non-conventional myosin motors and actin dynamics. Here authors use in vitro assays in which they observe that actin sliding on myosin 1b immobilized or bound to a fluid bilayer enhances actin depolymerization at the barbed end.

Cell membrane deformations are crucial for proper cell function. Specialized protein assemblies initiate inward or outward membrane deformations that the cell uses respectively to uptake external substances or probe the environment. The assembly and dynamics of the actin cytoskeleton are involved in this process, although their detailed role remains controversial. We show here that a dynamic, branched actin network is sufficient to initiate both inward and outward membrane deformation. The polymerization of a dense actin network at the membrane of liposomes produces inward membrane bending at low tension, while outward deformations are robustly generated regardless of tension. Our results shed light on the mechanism cells use to internalize material, both in mammalian cells, where actin polymerization forces are required when membrane tension is increased, and in yeast, where those forces are necessary to overcome the opposing turgor pressure. By combining experimental observations with physical modelling, we propose a mechanism that explains how membrane tension and the architecture of the actin network regulate cell-like membrane deformations. The same type of polymer network deforms cell membranes inward, to absorb external material, and outward, to facilitate signal transmission. Experiments and theory show that these deformations are regulated by membrane tension and network mesh size.

International audience; The internal and external mechanical environment plays an important role in tumorogenesis. As a proxy of an avas-cular early state tumor, we use multicellular spheroids, a composite material made of cells, extracellular matrix and permeating fluid. We characterize its effective rheology at the timescale of minutes to hours by compressing the aggregates with osmotic shocks and modeling the experimental results with an active poroelastic material that reproduces the stress and strain distributions in the aggregate. The model also predicts how the emergent bulk modulus of the aggregate as well as the hydraulic diffusion of the percolating interstitial fluid are modified by the preexisting active stress within the aggregate. We further show that the value of these two phenomenological parameters can be rationalized by considering that, in our experimental context, the cells are effectively impermeable and incompressible inclusions nested in a compressible and permeable matrix.

Cytoskeletal filaments assemble into dense parallel, antiparallel or disordered networks, providing a complex environment for active cargo transport and positioning by molecular motors. The interplay between the network architecture and intrinsic motor properties clearly affects transport properties but remains poorly understood. Here, by using surface micro-patterns of actin polymerization, we investigate stochastic transport properties of colloidal beads in antiparallel networks of overlapping actin filaments. We found that 200-nm beads coated with myosin-Va motors displayed directed movements towards positions where the net polarity of the actin network vanished, accumulating there. The bead distribution was dictated by the spatial profiles of local bead velocity and diffusion coefficient, indicating that a diffusion-drift process was at work. Remarkably, beads coated with heavy mero-myosin-II motors showed a similar behavior. However, although velocity gradients were steeper with myosin II, the much larger bead diffusion observed with this motor resulted in less precise positioning. Our observations are well described by a three-state model, in which active beads locally sense the net polarity of the network by frequently detaching from and reattaching to the filaments. A stochastic sequence of processive runs and diffusive searches results in a biased random walk. The precision of bead positioning is set by the gradient of net actin polarity in the network and by the run length of the cargo in an attached state. Our results unveiled physical rules for cargo transport and positioning in networks of mixed polarity.Significance statementCellular functions rely on small groups of molecular motors to transport their cargoes throughout the cell along polar filaments of the cytoskeleton. Cytoskeletal filaments self-assemble into dense networks comprising intersections and filaments of mixed polarity, challenging directed motor-based transport. Using micro-patterns of actin polymerization in-vitro, we investigated stochastic transport of colloidal beads in antiparallel networks of overlapping actin filaments. We found that beads coated with myosin motors sensed the net polarity of the actin network, resulting in active bead positioning to regions of neutral polarity with a precision depending on the motor type. A theoretical description of our experimental results provides the key physical rules for cargo transport and positioning in filament networks of mixed polarity.

In embryonic development or tumor evolution, cells often migrate collectively within confining tracks defined by their microenvironment 1,2. In some of these situations, the displacements within a cell strand are antiparallel 3, giving rise to shear flows. However, the mechanisms underlying these spontaneous flows remain poorly understood. Here, we show that an ensemble of spindle-shaped cells plated in a well-defined stripe spontaneously develop a shear flow whose characteristics depend on the width of the stripe. On wide stripes, the cells self-organize in a nematic phase with a director at a well-defined angle with the stripe’s direction, and develop a shear flow close to the stripe’s edges. However, on stripes narrower than a critical width, the cells perfectly align with the stripe’s direction and the net flow vanishes. A hydrodynamic active gel theory provides an understanding of these observations and identifies the transition between the non-flowing phase oriented along the stripe and the tilted phase exhibiting shear flow as a Fréedericksz transition driven by the activity of the cells. This physical theory is grounded in the active nature of the cells and based on symmetries and conservation laws, providing a generic mechanism to interpret in vivo antiparallel cell displacements.

Global changes of cell shape under mechanical or osmotic external stresses are mostly controlled by the mechanics of the cortical actin cytoskeleton underlying the cell membrane. Some aspects of this process can be recapitulated in vitro on reconstituted actin-and-membrane systems. In this paper, we investigate how the mechanical properties of a branched actin network shell, polymerized at the surface of a liposome, control membrane shape when the volume is reduced. We observe a variety of membrane shapes depending on the actin thickness. Thin shells undergo buckling, characterized by a cup-shape deformation of the membrane that coincides with the one of the actin network. Thick shells produce membrane wrinkles, but do not deform their outer layer. For intermediate micrometerthick shells, wrinkling of the membrane is observed, and the actin layer is slightly deformed. Confronting our experimental results with a theoretical description, we determine the transition between buckling and wrinkling depending on the thickness of the actin shell and the size of the liposome. We thus unveil the generic mechanism by which biomembranes are able to accommodate their shape against mechanical compression, through thickness adaptation of their cortical cytoskeleton.

A landmark of turbulence is the emergence of universal scaling laws, such as Kolmogorov's $E(q)\sim q^{-5/3}$ scaling of the kinetic energy spectrum of inertial turbulence with the wave vector $q$. In recent years, active fluids have been shown to exhibit turbulent-like flows at low Reynolds number. However, the existence of universal scaling properties in these flows has remained unclear. To address this issue, here we propose a minimal defect-free hydrodynamic theory for two-dimensional active nematic fluids at vanishing Reynolds number. By means of large-scale simulations and analytical arguments, we show that the kinetic energy spectrum exhibits a universal scaling $E(q)\sim q^{-1}$ at long wavelengths. We find that the energy injection due to activity has a peak at a characteristic length scale, which is selected by a nonlinear mechanism. In contrast to inertial turbulence, energy is entirely dissipated at the scale where it is injected, thus precluding energy cascades. Nevertheless, the non-local character of the Stokes flow establishes long-ranged velocity correlations, which lead to the scaling behavior. We conclude that active nematic fluids define a distinct universality class of turbulence at low Reynolds number., Comment: Updated journal version

We study experimentally and theoretically the thickness of the coating obtained by pulling out a rod from a reservoir of yield-stress fluid. Opposite to Newtonian fluids, the coating thickness for a fluid of large enough yield stress is determined solely by the flow inside the reservoir and not by the flow inside the meniscus. The stress field inside the reservoir determines the thickness of the coating layer. The thickness is observed to increase nonlinearly with the sizes of the rod and of the reservoir. We develop a theoretical framework that describes this behavior and allows us to precisely predict the coating thickness.

Pierre-Gilles de Gennes was one of the leading physical scientists of his generation. Awarded the Nobel Prize for physics in 1991, he made outstanding contributions to both solid state physics (magnetism, superconductivity) and so-called soft matter ( matière molle in French, a term he coined in his Nobel lecture), which includes among other systems polymers and liquid crystals. He was the first to realize the deep mathematical analogies that exist between these areas—for instance between polymers and magnetism, and (separately) between superconductors and liquid crystals. These abstract and surprising insights were those of a theorist par excellence , yet de Gennes was closely concerned with experiments throughout his career and was a sought-after contributor to industrial research. In several cases, such as his work on wetting and adhesion, de Gennes’s intense curiosity, combined with an unerring ability to detect weak points in the ‘received wisdom’, led him to rebuild the scientific knowledge base, with profound consequences for subsequent research in these areas.

Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal and pathological conditions 1–5. To perceive mechanical perturbations of different types and magnitudes, tissues need a range of appropriate detectors 6–8, with a compliance that has to match the perturbation amplitude. As a proxy of biological tissues, we use multicellular aggregates, a composite material made of cells, extracellular matrix and permeating fluid. We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9–13, while the same amount of selective compression on cells has almost no effect 14,15. We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space. This description correctly predicts the emergent bulk modulus of the aggregate as well as the hydrodynamic diffusion coefficient of the percolating interstitial fluid under compression. We further show that, on a longer timescale, the extracellular matrix serves as a sensor that regulates cell proliferation and migration in a 3D environment through its permanent deformation and dehydration following the global compression.