Biology subjects

Perez-Tirado, A.

Publications and source records attributed to Perez-Tirado, A..

3 recordsLinked to original sources

bioRxiv2025

Epithelial polarity drives tissue tension in planar, free standing cell monolayers

Polar epithelial cells form thin but resilient sheets that resist mechanical in-plane stress by relying on strong conformal contacts with each mediated by dedicated cell-cell connections connected to the viscoelastic cortex. In this study, we investigate the mechanical response of free-standing cell monolayers to central indentation as a function of orientation using a colloidal probe. We determine tissue tension by treating the deformed tissue as a minimal surface area. Our findings reveal that the cortex tension of the basal side governs the purely elastic response to in-plane extension, while the apical side of the cells is soft and dissipative giving rise to a hysteresis at low indentation depth. At larger indentation depth, the apico-basal polarity is no longer relevant as the cells are apically compressed and the response is driven by the elastic in-plane response of the basal side of the tissue. These results are particularly significant for lumen-forming epithelial cells, which experience substantial compressive forces especially apically due to elevated Laplace pressure.

biophysics↗

bioRxiv2025

The keratin cortex stabilizes cells at high strains

The eukaryotic cytoskeleton consists of three filament types: actin filaments, microtubules and intermediate filaments (IFs). IF proteins are expressed in a cell-type specific manner, and keratins are found in epithelial cells. In certain cell types, keratin forms a layer close to the membrane which may be referred to as an "IF-cortex". It is hypothesized that this IF-cortex arranges with radial bundles in a "rim-and-spokes" structure in epithelia. Based on this hypothesis, IFs and actin filaments might add complementary mechanical properties to the cortex. It was previously shown that single IFs in vitro remain undamaged at high strains and display a non-linear stretching behavior. We now ask the question of whether this unique force-extension behavior of single IFs is also relevant in the context of a filament network within a cell. We show that keratin-deficient (KO) MDCK II cells readily form 2D cell layers and 3D cysts and withstand high equibiaxial strains. High-resolution imaging using STED microscopy reveals altered actin cortex structures in KO cells, presumably in response to the missing keratin. We investigate the influence of the equibiaxial strain on the viscoelastic properties of wild-type (WT) and KO cells using atomic force microscopy. We find that the KO cells exhibit a higher pre-stress than the WT cells, likely due to the change of the cortical structure. Interestingly, both the pre-stress and the fluidity of the KO cells are altered already at intermediate strains, whereas the WT cells show a response only at high strain. Similarly, the KO cysts are stretched more easily at low strains than the WT cysts during injection experiments. The compressibility modulus is analyzed in a spatially resolved manner and we find this modulus to be increased at the cell rim, compared to the inside region, due to the geometry of the cell layer. Our results indicate that KO cells compensate for the missing keratin, but are nevertheless very sensitive to external strain, whereas the intricate interplay between the actin and keratin cortices in WT cells preserves the mechanical state and cell stability.

biophysics↗

bioRxiv2024

Mechanical Implications of Cellular Viscoelasticity, Cortex Polarity, Superelasticity, and Cell-Cell Junctions in Curved Tissues

Investigations of the response of curved epithelia derived from MDCK-II cells to external deformation involved indentation-relaxation experiments using colloidal probe microscopy. Notably, hemicysts exhibited lower tissue tension, greater compliance, and increased fluidity compared to cysts. The primary response to deformation turned out to be the in-plane expansion of the basal cortex/membrane of cells. Additionally, drug treatments applied to curved tissue, along with deformation of tailored mutants (such as E-cadherin knockout), revealed that tissue compliance over short time scales is influenced by an interplay of viscoelastic properties in individual cells, their apical-basal polarity, superelasticity of the shell, and excess interfacial area. Meanwhile, tissue resilience predominantly depends on the integrity of cell-cell contacts.

biophysics↗