Biology subjects

Wyatt, T. P. J.

Publications and source records attributed to Wyatt, T. P. J..

3 recordsLinked to original sources

bioRxiv2026

Basement membrane mechanics drives patterned response to developmental signalling

Precise spatiotemporal patterning of cell fate decisions during development, such as those accompanying gastrulation, has traditionally been attributed to morphogen gradients. Emerging evidence also points to a crucial role for mechanics in regulating cell fate decisions. Here, we uncover that basement membrane mechanics in human pluripotent stem cells (hPSCs) regulates the spatiotemporal response to gastrulation-inducing BMP4. Reducing mechanosensation via soft substrates or chemical inhibitors abolishes stereotypical spatial patterning of the BMP4 response in hPSC colonies. This loss arises from disrupted epithelial polarity and increased permeability, which enhance BMP receptor accessibility. Strikingly, apical exposure to soluble laminin similarly disrupts polarity and suppresses hPSC mechanosensing, phenocopying the soft substrates effect and suggesting feedback between polarity signaling and mechanosensing. Finally, softening the basement membrane in mouse embryos triggers ectopic and premature mesoderm differentiation, disrupting gastrulation patterning. Together, this study describes a mechanochemical feedback mechanism that establishes basement membrane mechanics as a key regulator of developmental patterning.

cell biology↗

bioRxiv2019

Curling of epithelial monolayers reveals coupling between active bending and tissue tension

Epithelial monolayers are two-dimensional cell sheets which compartmentalise the body and organs of multi-cellular organisms. Their morphogenesis during development or pathology results from patterned endogenous and exogenous forces and their interplay with tissue mechanical properties. In particular, bending of epithelia is thought to results from active torques generated by the polarization of myosin motors along their apico-basal axis. However, the contribution of these out-of-plane forces to morphogenesis remains challenging to evaluate because of the lack of direct mechanical measurement. Here, we use epithelial curling to characterize the out-of-plane mechan ics of epithelial monolayers. We find that curls of high curvature form spontaneously at the free edge of epithelial monolayers devoid of substrate in vivo and in vitro. Curling originates from an enrichment of myosin in the basal domain that generates an active spontaneous curvature. By measuring the force necessary to flatten curls, we can then estimate the active torques and the bending modulus of the tissue. Finally, we show that the extent of curling is controlled by the interplay between in-plane and out-of-plane stresses in the monolayer. Such mechanical coupling implies an unexpected role for in-plane stresses in shaping epithelia during morphogenesis.

biophysics↗

bioRxiv2018

Actomyosin controls planarity and folding of epithelia in response to compression

Throughout embryonic development and adult life, epithelia are subjected to external forces. The resulting deformations can have a profound impact on tissue development and function. These include compressive deformations which, although hard to study in model systems due to the confounding effects of the substrate, are thought to play an important role in tissue morphogenesis by inducing tissue folding and by triggering mechanosensitive responses including cell extrusion and cell differentiation. Here, using suspended epithelia, we are able to uncover the immediate response of epithelial tissues to the application of large (5-80%) in-plane compressive strains. We show that fast compression induces tissue buckling followed by active tissue flattening which erases the buckle within tens of seconds. Strikingly, there is a well-defined limit to this second response, so that stable folds form in the tissue for compressive strains larger than [~]35%. Finally, a combination of experiment and modelling shows that the response to compression is orchestrated by the automatic adaptation of the actomyosin cytoskeleton as it re-establishes tension in compressed tissues. Thus, tissue pre-tension allows epithelia to both buffer against fast compression and regulate folding.

biophysics↗