Biomimetic emulsions reveal the effect of homeostatic pressure on cell-cell adhesion

Cell-cell contacts in tissues are continuously subject to mechanical forces due to homeostatic pressure and active cytoskeleton dynamics. While much is known about the molecular pathways of adhesion, the role of mechanics is less well understood. To isolate the role of pressure we present a dense packing of functionalized emulsion droplets in which surface interactions are tuned to mimic those of real cells. By visualizing the microstructure in 3D we find that a threshold compression force is necessary to overcome electrostatic repulsion and surface elasticity and establish protein-mediated adhesion. Varying the droplet interaction potential maps out a phase diagram for adhesion as a function of force and salt concentration. Remarkably, fitting the data with our theoretical model predicts binder concentrations in the adhesion areas that are similar to those found in real cells. Moreover, we quantify the adhesion size dependence on the applied force and thus reveal adhesion strengthening with increasing homeostatic pressure even in the absence of active cellular processes. This biomimetic approach reveals the physical origin of pressure-sensitive adhesion and its strength across cell-cell junctions.Comment: 20 pages, 5 figure

Generalizable Denoising of Microscopy Images using Generative Adversarial Networks and Contrastive Learning

Microscopy images often suffer from high levels of noise, which can hinder further analysis and interpretation. Content-aware image restoration (CARE) methods have been proposed to address this issue, but they often require large amounts of training data and suffer from over-fitting. To overcome these challenges, we propose a novel framework for few-shot microscopy image denoising. Our approach combines a generative adversarial network (GAN) trained via contrastive learning (CL) with two structure preserving loss terms (Structural Similarity Index and Total Variation loss) to further improve the quality of the denoised images using little data. We demonstrate the effectiveness of our method on three well-known microscopy imaging datasets, and show that we can drastically reduce the amount of training data while retaining the quality of the denoising, thus alleviating the burden of acquiring paired data and enabling few-shot learning. The proposed framework can be easily extended to other image restoration tasks and has the potential to significantly advance the field of microscopy image analysis

Rejuvenation and overaging in a colloidal glass under shear

We report the modifications of the microscopic dynamics of a colloidal glass submitted to shear. We use multispeckle diffusing wave spectroscopy to monitor the evolution of the spontaneous slow relaxation processes after the sample have been submitted to various straining. We show that high shear rejuvenates the system and accelerates its dynamics whereas moderate shear overage the system. We analyze this phenomena within the frame of the Bouchaud's trap model.Comment: 4 pages, 4 figures, to be published in PR

Multispeckle diffusing-wave spectroscopy: a tool to study slow relaxation and time-dependent dynamics

A multispeckle technique for efficiently measuring correctly ensemble-averaged intensity autocorrelation functions of scattered light from non-ergodic and/or non-stationary systems is described. The method employs a CCD camera as a multispeckle light detector and a computer-based correlator, and permits the simultaneous calculation of up to 500 correlation functions, where each correlation function is started at a different time. The correlation functions are calculated in real time and are referenced to a unique starting time. The multispeckle nature of the CCD camera detector means that a true ensemble average is calculated; no time averaging is necessary. The technique thus provides a "snapshot" of the dynamics, making it particularly useful for non-stationary systems where the dynamics are changing with time. Delay times spanning the range from 1 ms to 1000 s are readily achieved with this method. The technique is demonstrated in the multiple scattering limit where diffusing-wave spectroscopy theory applies. The technique can also be combined with a recently-developed two-cell technique that can measure faster decay times. The combined technique can measure delay times from 10 ns to 1000 s. The method is peculiarly well suited for studying aging processes in soft glassy materials, which exhibit both short and long relaxation times, non-ergodic dynamics, and slowly-evolving transient behavior.Comment: 11 pages 13 figures Accepted in Review of Scientific Instrument (june 02

Loss of α-catenin elicits a cholestatic response and impairs liver regeneration

The liver is unique in its capacity to regenerate after injury, during which hepatocytes actively divide and establish cell-cell contacts through cell adhesion complexes. Here, we demonstrate that the loss of α-catenin, a well-established adhesion component, dramatically disrupts liver regeneration. Using a partial hepatectomy model, we show that regenerated livers from α-catenin knockdown mice are grossly larger than control regenerated livers, with an increase in cell size and proliferation. This increased proliferation correlated with increased YAP activation, implicating α-catenin in the Hippo/YAP pathway. Additionally, α-catenin knockdown mice exhibited a phenotype reminiscent of clinical cholestasis, with drastically altered bile canaliculi, elevated levels of bile components and signs of jaundice and inflammation. The disrupted regenerative capacity is a result of actin cytoskeletal disorganisation, leading to a loss of apical microvilli, dilated lumens in the bile canaliculi, and leaky tight junctions. This study illuminates a novel, essential role for α-catenin in liver regeneration

Membrane tension controls adhesion positioning at the leading edge of cells

Cell migration is dependent on adhesion dynamics and actin cytoskeleton remodeling at the leading edge. These events may be physically constrained by the plasma membrane. Here, we show that the mechanical signal produced by an increase in plasma membrane tension triggers the positioning of new rows of adhesions at the leading edge. During protrusion, as membrane tension increases, velocity slows, and the lamellipodium buckles upward in a myosin II-independent manner. The buckling occurs between the front of the lamellipodium, where nascent adhesions are positioned in rows, and the base of the lamellipodium, where a vinculin-dependent clutch couples actin to previously positioned adhesions. As membrane tension decreases, protrusion resumes and buckling disappears, until the next cycle. We propose that the mechanical signal of membrane tension exerts upstream control in mechanotransduction by periodically compressing and relaxing the lamellipodium, leading to the positioning of adhesions at the leading edge of cells

Influence d'un cisaillement oscillant sur la dynamique de vieillissement microscopique d'un verre colloidal

This experimental work tries to better characterize the eects of shearing upon the aging of colloidal glasses at a microscopic level. The rearrangement dynamics of the system is studied via a multiple light scattering technique (MSDWS) especially developed in this thesis. We show that under high oscillatory shear the system is rejuvenated and that it starts aging when the shear is stopped. Hence, at a microscopic level, high shear is equivalent for theses systems to thermal quench for other glassy materials. Furthermore we show that a gentle oscillatory shear help the system to age. We coined this phenomena "overaging". Theses two antagonistic eects (rejuvenation and overaging) are also observed on glassy polymer submitted to temperature steps. We eventually give a unied description of theses eects for the dierent perturbation within the frame of the SGR model. It clearly shows that an external perturbation broadens the distribution of relaxation for these systems.Ce travail expérimental cherche à mieux caractériser les effets du cisaillement sur le vieillissement d'un verre colloidal au niveau microscopique. La dynamique des réarrangements d'un tel système est étudiée au moyen d'une technique de diffusion multiple de la lumière (MSDWS) développée au cours de cette thèse. Nous montrons que la cessation d'un cisaillement de forte amplitude est, au niveau microscopique, l'équivalent pour ces systèmes d'une trempe thermique pour d'autres systèmes vitreux. Notre système est en effet rajeuni par un fort cisaillement puis présente un comportement de vieillissent classique à la cessation de celui-ci. De surcroît, nous montrons qu'un cisaillement de faible amplitude permet au système de vieillir plus vite. Nous appelons ce comportement le survieillissement. Ces deux effets antagonistes (rajeunissement et survieillissement) sont aussi observés sur des polymères vitreux soumis à des marches de température. Nous montrons enfin que le modèle SGR fournit une description unifiée de ces comportements similaires pour différents types de perturbation. Ceux-ci mettent en lumière l'élargissement de la distribution de temps de relaxation au sein de ce type de matériaux soumis à des perturbations extérieures