Src kinase slows collective rotation of confined epithelial cell monolayers.

Collective cell migration is key during development, wound healing, and metastasis and relies on coordinated cell behaviors at the group level. Src kinase is a key signalling protein for the physiological functions of epithelia, as it regulates many cellular processes, including adhesion, motility, and mechanotransduction. Its overactivation is associated with cancer aggressiveness.

Mechanical characterization of regenerating Hydra tissue spheres.

Hydra vulgaris, long known for its remarkable regenerative capabilities, is also a long-standing source of inspiration for models of spontaneous patterning. Recently it became clear that early patterning during Hydra regeneration is an integrated mechanochemical process whereby morphogen dynamics is influenced by tissue mechanics. One roadblock to understanding Hydra self-organization is our lack of knowledge about the mechanical properties of these organisms.

2.5D Traction Force Microscopy: Imaging three-dimensional cell forces at interfaces and biological applications.

The forces that cells, tissues, and organisms exert on the surface of a soft substrate can be measured using Traction Force Microscopy (TFM), an important and well-established technique in Mechanobiology. The usual TFM technique (two-dimensional, 2D TFM) treats only the in-plane component of the traction forces and omits the out-of-plane forces at the substrate interfaces (2.5D) that turn out to be important in many biological processes such as tissue migration and tumour invasion.

The effect of testosterone treatment on bone mineral density in Klinefelter syndrome: A retrospective cohort study.

Background: Although Klinefelter syndrome (KS) is the most frequent sex-hormone disorder, there is ongoing uncertainty about the often associated sex-hormone deficiency, its impact on common comorbidities, and therefore about prevention and treatment. In this study, we focus on bone loss, reported to occur in over 40% of KS patients, and the impact of testosterone replacement therapy (TRT) on this comorbidity.

Objectives: This single-center retrospective cohort study in a tertiary hospital compared the effect of treatment with TRT to no TRT on evolution of bone mineral density (BMD) in KS patients.

Mechanical stress driven by rigidity sensing governs epithelial stability.

Epithelia act as a barrier against environmental stress and abrasion and 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.

Mapping cell cortex rheology to tissue rheology and vice versa.

The mechanics of biological tissues mainly proceeds from the cell cortex rheology. A direct, explicit link between cortex rheology and tissue rheology remains lacking, yet would be instrumental in understanding how modulations of cortical mechanics may impact tissue mechanical behavior. Using an ordered geometry built on 3D hexagonal, incompressible cells, we build a mapping relating the cortical rheology to the monolayer tissue rheology.

All-in-one rheometry and nonlinear rheology of multicellular aggregates.

Tissues are generally subjected to external stresses, a potential stimulus for their differentiation or remodeling. While single-cell rheology has been extensively studied leading to controversial results about nonlinear response, mechanical tissue behavior under external stress is still poorly understood, in particular, the way individual cell properties translate at the tissue level. Herein, using magnetic cells we were able to form perfectly monitored cellular aggregates (magnetic molding) and to deform them under controlled applied stresses over a wide range of timescales and amplitudes (magnetic rheometer).

The impact of androgen deprivation therapy on bone mineral density in men treated for paraphilic disorder: A retrospective cohort study.

Background: Guidelines suggest treating men with paraphilic disorder with androgen-deprivation therapy (ADT). However, little evidence is available about the long-term impact on bone loss and how to manage this adverse event.

Objectives: The aim of this study is to assess the impact of ADT on bone mineral density (BMD) in men treated for paraphilic disorder with the androgen receptor blocker cyproterone acetate (CPA) and/or GnRH agonist triptoreline (GnRHa) and to evaluate the effect of treatment with bisphosphonates.

Enhanced RhoA signalling stabilizes E-cadherin in migrating epithelial monolayers.

Epithelia migrate as physically coherent populations of cells. Previous studies have revealed that mechanical stress accumulates in these cellular layers as they move. These stresses are characteristically tensile in nature and have often been inferred to arise when moving cells pull upon the cell-cell adhesions that hold them together.

Characterization of the Key Aroma Compounds in a Commercial Fino and a Commercial Pedro Ximénez Sherry Wine by Application of the Sensomics Approach.

Following the sensomics approach, the key aroma compounds of a commercial Fino and Pedro Ximénez sherry were identified, quantitated, and validated through recombination experiments. In Fino sherry, 31 compounds were determined in concentrations above their odor detection thresholds, with the fruity/green smelling 1,1-diethoxyethane displaying the highest odor activity value ((OAV); the ratio of the concentration to the odor threshold) of 8970, followed by ethyl (2,3)-hydroxy-3-methylpentanoate (853) and 2- and 3-methylbutanal (448). In the Pedro Ximénez sherry, 23 compounds were present in concentrations exceeding their odor thresholds, and the malty smelling 2- and 3-methylbutanal were found with the highest OAV (1006), followed by 1,1-diethoxyethane (808) and methylpropanal (561).

The role of single cell mechanical behavior and polarity in driving collective cell migration.

The directed migration of cell collectives is essential in various physiological processes, such as epiboly, intestinal epithelial turnover, and convergent extension during morphogenesis as well as during pathological events like wound healing and cancer metastasis. Collective cell migration leads to the emergence of coordinated movements over multiple cells. Our current understanding emphasizes that these movements are mainly driven by large-scale transmission of signals through adherens junctions.

Author Correction: An optochemical tool for light-induced dissociation of adherens junctions to control mechanical coupling between cells.

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

An optochemical tool for light-induced dissociation of adherens junctions to control mechanical coupling between cells.

The cadherin-catenin complex at adherens junctions (AJs) is essential for the formation of cell-cell adhesion and epithelium integrity; however, studying the dynamic regulation of AJs at high spatio-temporal resolution remains challenging. Here we present an optochemical tool which allows reconstitution of AJs by chemical dimerization of the force bearing structures and their precise light-induced dissociation. For the dimerization, we reconstitute acto-myosin connection of a tailless E-cadherin by two ways: direct recruitment of α-catenin, and linking its cytosolic tail to the transmembrane domain.

Testicular Vein Sampling Can Reveal Gonadotropin-Independent Unilateral Steroidogenesis Supporting Spermatogenesis.

Suppressed gonadotropins combined with high-normal serum testosterone concentrations in oligozoospermic men suggest either use of exogenous testosterone or presence of a testosterone-producing tumor. We describe the case of a 31-year-old man referred for primary infertility. Gonadotropins were undetectably low, but testosterone and estradiol were in the high-normal range.

Myosin II isoforms play distinct roles in junction biogenesis.

Adherens junction (AJ) assembly under force is essential for many biological processes like epithelial monolayer bending, collective cell migration, cell extrusion and wound healing. The acto-myosin cytoskeleton acts as a major force-generator during the de novo formation and remodeling of AJ. Here, we investigated the role of non-muscle myosin II isoforms (NMIIA and NMIIB) in epithelial junction assembly.

Sustained Oscillations of Epithelial Cell Sheets.

Morphological changes during development, tissue repair, and disease largely rely on coordinated cell movements and are controlled by the tissue environment. Epithelial cell sheets are often subjected to large-scale deformation during tissue formation. The active mechanical environment in which epithelial cells operate have the ability to promote collective oscillations, but how these cellular movements are generated and relate to collective migration remains unclear.

A Mechanosensitive RhoA Pathway that Protects Epithelia against Acute Tensile Stress.

Adherens junctions are tensile structures that couple epithelial cells together. Junctional tension can arise from cell-intrinsic application of contractility or from the cell-extrinsic forces of tissue movement. Here, we report a mechanosensitive signaling pathway that activates RhoA at adherens junctions to preserve epithelial integrity in response to acute tensile stress.

Kalman Inversion Stress Microscopy.

Although mechanical cues are crucial to tissue morphogenesis and development, the tissue mechanical stress field remains poorly characterized. Given traction force time-lapse movies, as obtained by traction force microscopy of in vitro cellular sheets, we show that the tissue stress field can be estimated by Kalman filtering. After validation using numerical data, we apply Kalman inversion stress microscopy to experimental data.

From cells to tissue: A continuum model of epithelial mechanics.

A two-dimensional continuum model of epithelial tissue mechanics was formulated using cellular-level mechanical ingredients and cell morphogenetic processes, including cellular shape changes and cellular rearrangements. This model incorporates stress and deformation tensors, which can be compared with experimental data. Focusing on the interplay between cell shape changes and cell rearrangements, we elucidated dynamical behavior underlying passive relaxation, active contraction-elongation, and tissue shear flow, including a mechanism for contraction-elongation, whereby tissue flows perpendicularly to the axis of cell elongation.

Cell growth, division, and death in cohesive tissues: A thermodynamic approach.

Cell growth, division, and death are defining features of biological tissues that contribute to morphogenesis. In hydrodynamic descriptions of cohesive tissues, their occurrence implies a nonzero rate of variation of cell density. We show how linear nonequilibrium thermodynamics allows us to express this rate as a combination of relevant thermodynamic forces: chemical potential, velocity divergence, and activity.

Emergence of epithelial cell density waves.

Epithelial cell monolayers exhibit traveling mechanical waves. We rationalize this observation thanks to a hydrodynamic description of the monolayer as a compressible, active and polar material. We show that propagating waves of the cell density, polarity, velocity and stress fields may be due to a Hopf bifurcation occurring above threshold values of active coupling coefficients.

Topological defects in epithelia govern cell death and extrusion.

Epithelial tissues (epithelia) remove excess cells through extrusion, preventing the accumulation of unnecessary or pathological cells. The extrusion process can be triggered by apoptotic signalling, oncogenic transformation and overcrowding of cells. Despite the important linkage of cell extrusion to developmental, homeostatic and pathological processes such as cancer metastasis, its underlying mechanism and connections to the intrinsic mechanics of the epithelium are largely unexplored.

Inference of Internal Stress in a Cell Monolayer.

We combine traction force data with Bayesian inversion to obtain an absolute estimate of the internal stress field of a cell monolayer. The method, Bayesian inversion stress microscopy, is validated using numerical simulations performed in a wide range of conditions. It is robust to changes in each ingredient of the underlying statistical model.

One-dimensional collective migration of a proliferating cell monolayer.

The importance of collective cellular migration during embryogenesis and tissue repair asks for a sound understanding of underlying principles and mechanisms. Here, we address recent in vitro experiments on cell monolayers, which show that the advancement of the leading edge relies on cell proliferation and protrusive activity at the tissue margin. Within a simple viscoelastic mechanical model amenable to detailed analysis, we identify a key parameter responsible for tissue expansion, and we determine the dependence of the monolayer velocity as a function of measurable rheological parameters.