Jacques Prost

Institut Curie · Département de Physicochimie du vivant

The number of cells in tissues is controlled by cell division and cell death, and its misregulation could lead to pathological conditions such as cancer. To maintain the cell numbers, a cell-elimination process called apoptosis also stimulates the proliferation of neighboring cells. This mechanism, apoptosis-induced compensatory proliferation, was...

Spatial organization of chromatin plays a critical role in genome regulation. Previously, various types of affnity mediators and enzymes have been attributed to regulate spatial organization of chromatin from a thermodynamics perspective. However, at the mechanistic level, enzymes act in their unique ways and perturb the chromatin. Here, we constru...

Epithelia act as barriers against environmental stresses. They are continuously exposed to various mechanical stress and abrasion, which impact epithelial integrity. The impact of the environment on epithelial integrity remains elusive. By culturing epithelial cells on two-dimensional hydrogels, we observe a loss of epithelial monolayer integrity o...

We show that dislocations in active two-dimensional (2D) smectic liquid crystals with underlying rotational symmetry are always unbound in the presence of noise, meaning the active smectic phase does not exist for nonzero noise in d=2. The active smectic phase can, like equilibrium smectics in 2D, be stabilized by applying rotational symmetry-break...

Fluid pumping and the generation of electric current by living tissues are required during morphogenetic processes and for maintainance of homeostasis. How these flows emerge from active and passive ion transport in cells has been well established. However, the interplay between flow and current generation is not well understood. Here, we study the...

Three-dimensional collective epithelial rotation around a given axis represents a coordinated cellular movement driving tissue morphogenesis and transformation. Questions regarding these behaviors and their relationship with substrate curvatures are intimately linked to spontaneous active matter processes and to vital morphogenetic and embryonic pr...

Cell monolayers are a central model system in the study of tissue biophysics. In vivo, epithelial tissues are curved on the scale of microns, and the curvature’s role in the onset of spontaneous tissue flows is still not well understood. Here, we present a hydrodynamic theory for an apical-basal asymmetric active nematic gel on a curved strip. We s...

Tissue layers can generally slide at the interface, accompanied by the dissipation due to friction. Nevertheless, it remains elusive how force could propagate in a tissue with such interfacial friction. Here, we elaborate the force dynamics in a prototypical multilayer system in which an epithelial monolayer was cultivated upon an elastic substrate...

We derive a fully covariant theory of the hydrodynamics of nematic and polar active surfaces, subjected to internal and external forces and torques. We study the symmetries of polar and nematic surfaces and find that in addition to five different types of in-plane isotropic surfaces, polar and nematic surfaces can be classified into five polar, two...

Alcanivorax borkumensis are prominent actors in oil spill bioremediation; however, the interfacial dynamics of their biofilms and its role in oil degradation remain unclear. Longitudinal tracking of biofilm-covered oil microdroplets using microfluidics reveals a spontaneous morphological transition from a thick biofilm phenotype to a thin dendritic...

Studies of electric effects in biological systems, from the work on action potential to studies on limb regeneration or wound healing, commonly focus on transitory behaviour and not on addressing the question of homeostasis. Here we use a microfluidic device to study how the homeostasis of confluent epithelial tissues is modified when a transepithe...

We show that dislocations in active 2d smectics with underlying rotational symmetry are always unbound in the presence of noise, meaning the active smectic phase does not exist for non-zero noise in $d=2$. The active smectic phase can, like equilibrium smectics in 2d, be stabilized by applying rotational symmetry breaking fields; however, even in t...

Epithelia act as a barrier against environmental stress and abrasion and in vivo they are continuously exposed to environments of various mechanical properties. The impact of this environment on epithelial integrity remains elusive. By culturing epithelial cells on 2D hydrogels, we observe a loss of epithelial monolayer integrity through spontaneou...

Cell monolayers are a central model system to tissue biophysics. In vivo, epithelial tissues are curved on the scale of microns, and curvature's role in the onset of spontaneous tissue flows is still not well-understood. Here, we present a hydrodynamic theory for an apical-basal asymmetric active nematic gel on a curved strip. We show that surface...

We derive a fully covariant theory of the hydrodynamics of nematic and polar active surfaces, subjected to internal and external forces and torques. We study the symmetries of polar and nematic surfaces and find that in addition to 5 different types of in-plane isotropic surfaces, polar and nematic surfaces can be classified into 5 polar, 2 pseudop...

Spatial organization of chromatin plays a critical role in genome regulation. Various types of affinity mediators and enzymes have been attributed to regulate spatial organization of chromatin from a thermodynamics perspective. However, at the mechanistic level, enzymes act in their unique ways. Here, we construct a polymer physics model following...

Studies of electric effects in biological systems, from the historical experiments of Galvani ¹ and the ground-breaking work on action potential ² to studies on limb regeneration ³ or wound healing ⁴ , share the common feature of being concerned with transitory behavior and not addressing the question of homeostasis. Here using a novel microfluidic...

Cells in a tissue mutually coordinate their behaviors to maintain tissue homeostasis and control morphogenetic dynamics. As well as chemical signals, mechanical entities such as force and strain can be possible mediators of the signalling cues for this mutual coordination, but how such mechanical cues can propagate has not been fully understood. He...

The number of cells in tissues is tightly controlled by cell division and cell death, and misregulation of cell numbers could lead to pathological conditions such as cancer. To maintain cell numbers in a tissue, a cell elimination process named programmed cell death or apoptosis, stimulates the proliferation of neighboring cells. This mechanism is...

Significance In addition to generating forces and reacting to mechanical cues, tissues are capable of actively pumping fluid and creating electric current. In this work, we examine how a hydraulic or electrical perturbation, imposed, for instance, by a drain of micrometric diameter, can be used to perturb tissue growth. We address this issue in a c...

We analyse the stem cell nucleus shape fluctuation spectrum obtained from optical confocal microscopy on an hour time scale with 10 s resolution. In particular, we investigate the angular and time dependencies of these fluctuations, define appropriate correlation functions that reveal the fundamentally out of equilibrium nature of the observed fluc...

We use a theoretical approach to examine the effect of a radial fluid flow or electric current on the growth and homeostasis of a cell spheroid. Such conditions may be generated by a drain of micrometric diameter. To perform this analysis, we describe the tissue as a continuum. We include active mechanical, electric, and hydraulic components in the...

We present a minimal model to study the effects of pH on liquid phase separation of macromolecules. Our model describes a mixture composed of water and macromolecules that exist in three different charge states and have a tendency to phase separate. This phase separation is affected by pH via a set of chemical reactions describing protonation and d...

We calculate the Casimir stresses in a thin layer of active fluid with nematic order. By using a stochastic hydrodynamic approach for an active fluid layer of finite thickness L, we generalize the Casimir stress for nematic liquid crystals in thermal equilibrium to active systems. We show that the active Casimir stress differs significantly from it...

The simplest extensions of single-particle dynamics in a momentum-conserving active fluid-an active suspension of two colloidal particles or a single particle confined by a wall-exhibit strong departures from Boltzmann behavior, resulting in either a breakdown of an effective temperature description or a steady state with nonzero-entropy production...

Significance How do tissues self-organize to generate the complex organ shapes observed in vertebrates? Organ formation requires the integration of chemical and mechanical information, yet how this is achieved is poorly understood for most organs. Muscle compartments in zebrafish display a V shape, which is believed to be required for efficient swi...

We present a minimal model to study liquid phase separation in a fixed pH ensemble. The model describes a mixture composed of macromolecules that exist in three different charge states and have a tendency to phase separate. We introduce the pH dependence of phase separation by means of a set of reactions describing the protonation and deprotonation...

Significance The presence of fluid-filled cavities is a common feature of multicellular structures. Nucleation and growth of such lumens typically involve the pumping of fluid by cells, which relies on active ion transport. In this paper, we use a continuum description of a spherical cell assembly that takes into account fluid pumping, electric cur...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Axonal beading, or the formation of a series of swellings along the axon, and retraction are commonly observed shape transformations that precede axonal atrophy in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. The mechanisms driving these morphological transformations are poorly understood. Here, we report contro...

Cells sense the rigidity of their environment through localized pinching, which occurs when myosin molecular motors generate contractions within actin filaments anchoring the cell to its surroundings. We present high-resolution experiments performed on these elementary contractile units in cells. Our experimental results challenge the current under...

We discuss the physical mechanisms that promote or suppress the nucleation of a fluid-filled lumen inside a cell assembly or a tissue. We discuss lumen formation in a continuum theory of tissue material properties in which the tissue is described as a two-fluid system to account for its permeation by the interstitial fluid, and we include fluid pum...

We calculate the Casimir stresses in a thin layer of active fluid with nematic order. By using a stochastic hydrodynamic approach for an active fluid layer of finite thickness $L$, we generalize the Casimir stress for nematic liquid crystals in thermal equilibrium to active systems. We show that the active Casimir stress differs significantly from...

We present a theoretical study of the dynamics of a thick polar epithelium subjected to the action of both an electric and a flow field in a planar geometry. We develop a generalized continuum hydrodynamic description and describe the tissue as a two component fluid system. The cells and the interstitial fluid are the two components and we keep all...

Axonal beading--formation of a series of swellings along the axon--and retraction are commonly observed shape transformations that precede axonal atrophy in Alzheimer's, Parkinson, and other neurodegenerative conditions. The mechanisms driving these morphological transformations are poorly understood. Here we report controlled experiments which can...

Organ formation is an inherently biophysical process, requiring large-scale tissue deformations. Yet, understanding how complex organ shape emerges during development remains a major challenge. During fish embryogenesis, large muscle segments, called myotomes, acquire a characteristic chevron morphology, which is believed to play a role in swimming...

We study the dynamics of a thick polar epithelium subjected to the action of both an electric and a flow field in a planar geometry. We develop a generalized continuum hydrodynamic description and describe the tissue as a two component fluid system. The cells and the interstitial fluid are the two components and we keep all terms allowed by symmetr...

We study the dynamics of a thick polar epithelium subjected to the action of both an electric and a flow field in a planar geometry. We develop a generalized continuum hydrodynamic description and describe the tissue as a two component fluid system. The cells and the interstitial fluid are the two components and we keep all terms allowed by symmetr...

We theoretically explore fluidization of epithelial tissues by active T1 neighbor exchanges. We show that the geometry of cell-cell junctions encodes important information about the local features of the energy landscape, which we support by an elastic theory of T1 transformations. Using a 3D vertex model, we show that the degree of active noise dr...

Simplest extensions of single particle dynamics in momentum conserving active fluid - that of an active suspension of two colloidal particles or a single particle confined by a wall - exhibit strong departures from Boltzmann behavior, resulting in either a breakdown of an effective temperature description or a steady state with nonzero entropy prod...

In embryonic development or tumour evolution, cells often migrate collectively within confining tracks defined by their microenvironment1,2. In some of these situations, the displacements within a cell strand are antiparallel³, giving rise to shear flows. However, the mechanisms underlying these spontaneous flows remain poorly understood. Here, we...

We theoretically explore fluidization of epithelial tissues by active T1 neighbor exchanges. We show that the geometry of cell-cell junctions encodes important information about the local features of the energy landscape, which we support by an elastic theory of T1 transformations. Using a 3D vertex model, we study tissue response to in-plane shear...

We theoretically explore fluidization of epithelial tissues by active T1 neighbor exchanges. We show that the geometry of cell-cell junctions encodes important information about the local features of the energy landscape, which we support by an elastic theory of T1 transformations. Using a 3D vertex model, we study tissue response to in-plane shear...

We model the dynamics of formation of intercellular secretory lumens. Using conservation laws, we quantitatively study the balance between paracellular leaks and the build-up of osmotic pressure in the lumen. Our model predicts a critical pumping threshold to expand stable lumens. Consistently with experimental observations in bile canaliculi, the...

Significance The development of intercellular cavities (lumens) is a ubiquitous mechanism to form complex tissue structures in organisms. The generation of Ciona Notochord, the formation of Zebrafish vasculature, or the formation of bile canaliculi between hepatic cells constitute a few examples. Lumen growth is governed by water intake that usuall...

We present high resolution experiments performed on elementary contractile units in cells that challenge our current understanding of molecular motor force generation. The key features are the development of a force per motor considerably larger than forces measured in single molecule experiments, a force increase followed by relaxation controlled...

Movie S1. EndoA2 N-BAR Domain Does Not Induce Scission of Tubular Membranes, Related to Figure 1 and Figure S1 Confocal fluorescence time-lapse during injection of an N-BAR domain of endoA2 near a tube pulled from a micropipette-aspired GUV. Movie shows spontaneous tubulation of the GUV and the formation of a scaffold on the tube (causing it to bu...

Confocal fluorescence time lapse showing a scission event of a kinesin-pulled tube connected to a GUV seconds after endoA2 injection into the system. Shown is a different example from Movie S4. Scale bar, 2 μm.

Movie shows extension of a tube partially scaffolded by endoA2 N-BAR domain leading up to scission at the tube-GUV interface. Shown are the confocal fluorescence time lapse (left) and the tube retraction force, f, both changing with time, t. Top left: N-BAR (green); center left: lipids (red); bottom left: overlay

Movie shows extension of a tube initially fully scaffolded by endoA2 N-BAR domain leading up to scission. After initial extension, gaps form in the scaffold making fully and partially scaffolded tubes equivalent in FDS. Shown are confocal fluorescence time lapse (left) and tube retraction force, f, both changing with time, t. Top left: N-BAR (green...

Confocal fluorescence time lapse showing two scission events of kinesin-pulled tubes connected to a GUV seconds after endoA2 injection into the system. Scale bar, 2 μm.

Membrane scission is essential for intracellular trafficking. While BAR domain proteins such as endophilin have been reported in dynamin-independent scission of tubular membrane necks, the cutting mechanism has yet to be deciphered. Here, we combine a theoretical model, in vitro, and in vivo experiments revealing how protein scaffolds may cut tubul...

We investigate the effect of stress fluctuations on the stochastic dynamics of an inclusion embedded in a viscous gel. We show that, in non-equilibrium systems, stress fluctuations give rise to an effective attraction towards the boundaries of the confining domain, which is reminiscent of an active Casimir effect. We apply our result to the dynamic...

We study stochastic dynamics of an inclusion within a one dimensional confined viscous active fluid. To highlight various features and to appeal to different contexts, the inclusion is in turn treated as a rigid element, an elastic element and a viscoelastic (Kelvin-Voigt) element. We show that the dynamics for the shape and position of the inclusi...

The surrounding microenvironment limits tumour expansion, imposing a compressive stress on the tumour, but little is known how pressure propagates inside the tumour. Here we present non-destructive cell-like microsensors to locally quantify mechanical stress distribution in three-dimensional tissue. Our sensors are polyacrylamide microbeads of well...

Supplementary Figures, Supplementary Notes and Supplementary References.

Supplementary Movie 1 Internalization of Polyacrylamide beads within multicellular-spheroids. Polyacrylamide beads functionalized with fibronectin were added to the culture media during the first stage of spheroid formation (time 00:00) which relies on the cells aggregation. Arrows indicate the position of the bead. Scale bar 200µm. Time scale in h...

According to the physicist Richard Feynman, a system is in equilibrium when “all the fast things have happened but the slow things have not” (1). This definition really applies to a system at steady state, which can either be in thermodynamic equilibrium or in a nonequilibrium steady state. Most systems in nature are not in equilibrium; they exchan...

E. Muto, et al. reported in 2005 an observation called cooperative binding, according to which the initial binding of a bead covered with active kinesins on a microtubule filament was capable of favoring the subsequent binding of similar beads on the same filament up to distances of the order of a few microns. This positive bias is stronger ahead o...

We study the surface fluctuations of a tissue with a dynamics dictated by cell-rearrangement, cell-division and cell-death processes. Surface fluctuations are calculated in the homeostatic state, where cell division and cell death equilibrate on average. The obtained fluctuation spectrum can be mapped onto several other spectra such as those charac...

We use the theory of active gels to study theoretically the merging and separation of two actin dense layers akin to cortical layers of animal cells. The layers bind at a distance equal to twice the thickness of a free layer, thus forming a single dense layer, similar in this sense to a lamellipodium. When that unique layer is stretched apart, it i...

Mechanical properties of cell membranes are known to be significantly influenced by the underlying cortical cytoskeleton. The technique of pulling membrane tethers from cells is one of the most effective ways of studying the membrane mechanics and the membrane-cortex interaction. In this article, we show that axon membranes make an interesting syst...