Biology subjects

Prost, J.

Publications and source records attributed to Prost, J..

11 recordsLinked to original sources

bioRxiv2026

Morphogenesis of a stratified cell mound at a vortex defect

Although topological defects in cell monolayers have been recognized as mechanical organizing centers in morphogenetic processes, the mechanism by which cells coordinate their motion at such defects and self-organize into higher-order structures remains elusive. Here, we report the formation of three-dimensional (3D) multicellular mounds in unconfined myoblast monolayers, at well-controlled vortex topological defects. Prior to the onset of bilayering, the vortex structure induces millimeter-scale cell flows converging toward the defect center. As a result, 3D cell mounds form at the defect core, layer-by-layer. These mounds grow by interlayer permeation sustained by the converging cell flows. At late stages, the bell shape of the structured mounds can be modeled with a dynamics driven by these converging flows. Our results therefore highlight the crucial role of integer topological defects in driving large-scale cell flows yielding the formation of highly ordered 3D tissues from a monolayer. We propose that similar mechanisms may be at play in certain morphogenetic and tumorigenic events.

biophysics↗

bioRxiv2025

Fibrillar adhesions are the primary integrin complexes shaped by matrix topography

Mechanisms of matrix topography recognition are poorly understood. Here, we show that 5{beta}1-integrin mediated fibrillar adhesions serve this function. While on planar substrates, their formation requires fibronectin secretion, tensins, and actomyosin contractility, these requirements are bypassed on nanotopographical features. While focal adhesions avoid these features, fibrillar adhesions rapidly align along pre-existing fibrous cell-derived matrix or electrospun nanofibers where they can then template fibronectin fibrils. Topography-induced fibrillar adhesions depend primarily on 5{beta}1-integrin clustering and disassemble upon cortical stiffening driven by myosin-II overactivation or increased membrane tension. We propose a generic theoretical model where the adhesion receptor favours the membrane and substrate planes to be tilted relative to each other. This model matches experimental observations of preferential 5{beta}1-integrin clustering along nanofibers and concave edges of large negative curvature along micro-ridges. These findings establish fibrillar adhesions as primary adhesion complexes that form independently of focal adhesions in response to matrix topography.

cell biology↗

bioRxiv2025

Regulation of epithelial tissue homeostasis by active trans-epithelial transport

Epithelia are intricate tissues whose function is intimately linked to mechanics. While mechanobiology has primarily focused on factors such as cell-generated contractility and mechanical properties of extracellular matrix (ECM), a novel mechanobiological paradigm highlights the role of osmotic and mechanical pressures in shaping epithelial tissues. In our study, we developed an in vitro model of cell coated micro-sized hydrogel spheres (MHSs) which allows to decipher the interplay between cellular activities and tissue mechanics. Drastic, isotropic MHS compressions were observed once the epithelia reached confluence. Further studies revealed that the compression was a process independent of cell contractility but rather regulated by active transepithelial fluid flow. Compressive stresses of about 7 kPa are generated by such an active hydraulic mechanism. Tissue homeostasis is then maintained by a fine balance between cell proliferation and extrusion. Our findings demonstrate the critical role of fluid transport in generating mechanical forces within epithelial tissues. Supported by a theoretical mechano-hydraulic model, a mechanistic framework for understanding the intricate interplay between cellular processes and tissue mechanics was established. These results challenge traditional views of epithelial tissue mechanics, emphasizing the pivotal influence of osmotic and mechanical pressures in shaping tissues. We anticipate that this study will advance the understanding of epithelial tissue development, the maintenance of homeostasis, and the mechanisms underlying pathological conditions. Significance StatementEpithelial tissues are vital for many bodily functions, but their mechanics remain poorly understood. Our study uncovers a novel mechanism by which epithelial cells generate mechanical stress, not through traditional cell contractility, but by actively pumping ions and water across their membranes. Using a model of micro-sized hydrogel spheres (MHSs) coated with epithelial cells, we demonstrate that epithelial cells actively transport fluid across the tissue to compress the MHSs. This facilitates the establishment of tissue homeostasis, which is further maintained by a balanced cell proliferation and extrusion rate. Supported by a theoretical model, our findings highlight the overlooked role of fluid transport in tissue mechanics, offering new insights into how epithelial tissues develop, maintain stability, and respond to disease.

cell biology↗

bioRxiv2022

Alcanivorax borkumensis Biofilms Enhance Oil Degradation By Interfacial Tubulation

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 phenotype optimized for high oil consumption rates. We show experimentally that biofilm dendrites emerge from aster-like nematic defects in the thin biofilms. We develop a theoretical model that elucidates the transition between phenotypes, linking tubulation to decreased interfacial tension and increased cell hydrophobicity, which we verify experimentally. We demonstrate positional control over the nematic defects on the droplets using microfluidics, causing the biofilm to dimple the droplets. Our results reveal how A. borkumensis biofilms utilize topological defects to increase oil access to achieve superior oil consumption rates, which may be a general strategy in oil-consuming bacteria. ONE SENTENCE SUMMARYA. borkumensis adapt their interfacial properties over time to evolve their biofilm phenotype and increase their oil consumption

biophysics↗

bioRxiv2022

Mechanical stress driven by rigidity sensing governs epithelial stability

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 spontaneous hole formation when grown on soft substrates. Substrate stiffness triggers an unanticipated mechanical switch of epithelial monolayers from tensile on soft to compressive on stiff substrates. Through active nematic modelling, we find unique patterns of cell shape texture called nematic topological defects that underpin large isotropic stress fluctuations at certain locations thereby triggering mechanical failure of the monolayer and hole opening. Our results show that substrate stiffness provides feedback on monolayer mechanical state and that topological defects can trigger stochastic mechanical failure, with potential application towards a mechanistic understanding of compromised epithelial integrity in bacterial infection, tumor progression and morphogenesis.

biophysics↗

bioRxiv2021

Mechanics defines the spatial pattern of compensatory proliferation

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 called apoptosis-induced compensatory proliferation, which was originally reported more than 40 years ago. While only a limited number of the neigboring cells need to divide to compensate for apoptotic cell loss, the mechanisms that select cells for undergoing division remain an open question. Here we found that the spatial inhomogeneity in mechanotransduction through a growth-promoting transcription co-activator Yes-associated protein (YAP) in the neighboring tissue, accounts for the inhomogeneity of compensatory proliferation. Such inhomogeneous mechanotransduction arises from the combination of the non-uniform distribution of nuclear size, which is inherent in tissues, and the non-uniform pattern of mechanical force applied to the neighboring cells upon apoptosis. Our findings from a mechanical perspective complement the current biochemical understanding of compensatory growth and provide additional insights into cellular functions of how tissue precisely maintains its homeostasis.

cell biology↗

bioRxiv2019

The roles of microtubules and membrane tension in axonal beading, retraction, and atrophy

Axonal beading--formation of a series of swellings along the axon--and retraction are commonly observed shape transformations that precede axonal atrophy in Alzheimers, Parkinson, and other neurodegenerative conditions. The mechanisms driving these morphological transformations are poorly understood. Here we report controlled experiments which can induce either beading or retraction and follow the time evolution of these responses. By making quantitative analysis of the shape modes under different conditions, measurement of membrane tension, and using theoretical considerations, we argue that membrane tension is the main driving force that pushes cytosol out of the axon when microtubules are degraded, causing axonal thinning. Under pharmacological perturbation, atrophy is always retrograde and this is set by a gradient in the microtubule stability. The nature of microtubule depolymerization dictates the type of shape transformation vis a vis beading or retraction. Elucidating the mechanisms of these shape transformations will facilitate development of strategies to prevent or arrest axonal atrophy due to neurodegenerative conditions.

biophysics↗

bioRxiv2018

Shaping the zebrafish myotome by differential friction and active stress

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. The final myotome shape can be altered by perturbing muscle cell differentiation or by altering the interaction between myotomes and surrounding tissues during morphogenesis. To disentangle the mechanisms contributing to shape formation of the myotome, we combine single-cell resolution live imaging with quantitative image analysis and theoretical modeling. We find that, soon after its segmentation from the presomitic mesoderm, the future myotome spreads across the underlying tissues. The mechanical coupling between the myotome and the surrounding tissues is spatially varying, resulting in spatially heterogeneous friction. Using a vertex model, we show that the interplay of differential spreading and friction is sufficient to drive the initial phase of myotome shape formation. However, we find that active stresses, generated during muscle cell differentiation, are necessary to reach the acute angle of the myotome observed in wildtype embryos. A final ingredient for formation and maintenance of the chevron shape is tissue plasticity, which is mediated by orientated cellular rearrangements. Our work sheds a new light on how a spatio-temporal sequence of local cellular events can have a non-local and irreversible mechanical impact at the tissue scale, leading to robust organ shaping.

biophysics↗

bioRxiv2018

Field induced cell proliferation and death in a thick epithelium

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 symmetry. In particular we keep track of the cell pumping activity for both solvent flow and electric current and discuss the corresponding orders of magnitude. We study the growth dynamics of tissue slabs, their steady states and obtain the dependence of the cell velocity, net cell division rate, and cell stress on the flow strength and the applied electric field. We find that finite thickness tissue slabs exist only in a restricted region of phase space and that relatively modest electric fields or imposed external flows can induce either proliferation or death.

biophysics↗

bioRxiv2018

Myosin filaments reversibly generate large forces in cells

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 by a characteristic displacement rather than by a characteristic force, the observation of steps at half the actin filament period even though a large number of motors are at work in an elementary contractile unit. We propose a generic two-state model of molecular motor collections with hand-over-hand contractions and we find that these unexpected observations are spontaneously emerging features of a collective motor behavior.

biophysics↗

bioRxiv2018

Physics of lumen growth

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 model also describes a transition between a monotonous and oscillatory regime during luminogenesis as a function of ion and water transport parameters. We finally discuss the possible importance of regulation of paracellular leaks in intercellular tubulogenesis.

biophysics↗