Biology subjects

Arroyo, M.

Publications and source records attributed to Arroyo, M..

4 recordsLinked to original sources

bioRxiv2022

The laminin-keratin link shields the nucleus from mechanical deformation and signalling

The mechanical properties of the extracellular matrix (ECM) dictate tissue behaviour. In epithelial tissues, laminin is both a very abundant ECM component, and a key supporting element. Here we show that laminin hinders the mechanoresponses of breast epithelial cells by shielding the nucleus from mechanical deformation. Coating substrates with laminin-111, unlike fibronectin or collagen I, impairs cell response to substrate rigidity, and YAP nuclear localization. Blocking the laminin-specific integrin {beta}4 increases nuclear YAP ratios in a rigidity dependent manner, without affecting cell forces or focal adhesions. By combining mechanical perturbations and mathematical modelling, we show that {beta}4 integrins establish a mechanical linkage between the substrate and the keratin cytoskeleton, which stiffens the network and shields the nucleus from actomyosin-mediated mechanical deformation. In turn, this affects nuclear YAP mechanoresponses and chromatin methylation. Our results demonstrate a mechanism by which tissues can regulate their sensitivity to mechanical signals.

cell biology↗

bioRxiv2021

A mechanosensing mechanism mediated by IRSp53 controls plasma membrane shape homeostasis at the nanoscale

As cells migrate and experience forces from their surroundings, they constantly undergo mechanical deformations which reshape their plasma membrane (PM). To maintain homeostasis, cells need to detect and restore such changes, not only in terms of overall PM area and tension as previously described, but also in terms of local, nano-scale topography. Here we describe a novel phenomenon, by which cells sense and restore mechanically induced PM nano-scale deformations. We show that cell stretch and subsequent compression reshape the PM in a way that generates local membrane evaginations in the 100 nm scale. These evaginations are recognized by the I-BAR protein IRSp53, which triggers a burst of actin polymerization mediated by Rac1 and Arp2/3. The actin polymerization burst subsequently re-flattens the evagination, completing the mechanochemical feedback loop. Our results demonstrate a new mechanosensing mechanism for PM shape homeostasis, with potential applicability in different physiological scenarios. TeaserCell stretch cycles generate PM evaginations of {approx}100 nm which are sensed by IRSp53, triggering a local event of actin polymerization that flattens and recovers PM shape.

biophysics↗

bioRxiv2020

Dynamic Mechanochemical feedback between curvedmembranes and BAR protein self-organization

In many physiological situations, BAR proteins interact with, and reshape, pre-existing curved membranes, contributing to essential cellular processes. However, the non-equilibrium and timedependent process of reshaping, and its dependence on initial membrane shape, remains largely unknown. Here we explain, both experimentally and through modelling, how a BAR protein dynamically interacts with mechanically bent lipid membranes. We capture protein binding to curved membranes, and characterize a variety of dynamical reshaping events depending on membrane shape and protein arrangement. The events can be generally understood by an isotropic-to-nematic phase transition, in which low curvature templates with isotropic protein orientation progress towards highly curved lipid tubes with nematic protein arrangement. Our findings also apply in cells, where mechanical stretch triggers BAR-protein-membrane interactions that enable potential mechanotransduction mechanisms. Our results characterize and broaden the reshaping processes of BAR proteins on mechanically constrained membranes, demonstrating the interplay between membrane mechanical stimuli and BAR protein response.

biophysics↗

bioRxiv2020

Mechanical compartmentalization of the intestinal organoid enables crypt folding and collective cell migration

Intestinal organoids capture essential features of the intestinal epithelium such as folding of the crypt, spatial compartmentalization of different cell types, and cellular movements from crypt to villus-like domains. Each of these processes and their coordination in time and space requires patterned physical forces that are currently unknown. Here we map the three-dimensional cell-ECM and cell-cell forces in mouse intestinal organoids grown on soft hydrogels. We show that these organoids exhibit a non-monotonic stress distribution that defines mechanical and functional compartments. The stem cell compartment pushes the ECM and folds through apical constriction, whereas the transit amplifying zone pulls the ECM and elongates through basal constriction. Tension measurements establish that the transit amplifying zone isolates mechanically the stem cell compartment and the villus-like domain. A 3D vertex model shows that the shape and force distribution of the crypt can be largely explained by cell surface tensions following the measured apical and basal actomyosin density. Finally, we show that cells are pulled out of the crypt along a gradient of increasing tension, rather than pushed by a compressive stress downstream of mitotic pressure as previously assumed. Our study unveils how patterned forces enable folding and collective migration in the intestinal crypt.

cell biology↗