Biology subjects

Tetley, R. J.

Publications and source records attributed to Tetley, R. J..

4 recordsLinked to original sources

bioRxiv2025

Three-Dimensional Mechanical Cooperativity Optimises Epithelial Wound Healing

Epithelial tissues serve as critical physical barriers that protect organs, making efficient repair essential upon damage. To achieve this, tissues must quickly react, forcing cells to rearrange and accommodate. Therefore, cells must cope with forces that will deform their shape to achieve these sudden but necessary changes. In the Drosophila wing disc, we showed how tissue fluidisation accelerated wound healing in 2D. However, the 3D aspect of tissue repair remains poorly understood. Here, we uncover a new mechanism aiding the tissue in repairing itself by changing cell height. We find actomyosin contractile cables at the wound edge connecting the apical and basal cell surface, which indent the apical side of the tissue and deform the basement membrane (BM), respectively. To understand the role of the different repair mechanisms, we developed a 3D vertex model allowing apico-basal intercalations. The model predicts that lateral cables play a role in regulating cell-cell intercalations, confirmed by Drosophila mutations affecting cell deformations. Our results demonstrate that lateral cables cooperate with the apical purse string to drive 3D cell shape changes and intercalations to promote more efficient wound repair.

developmental biology↗

bioRxiv2021

Mechanical Forces during Lymph Node Expansion Govern Fibroblastic Reticular Network Remodeling

Emergent physical properties of tissues are not readily understood by reductionist studies of their constituent cells. Here, we show molecular signals controlling cellular physical properties, collectively determining tissue mechanics of lymph nodes, an immunologically-relevant, adult mammalian tissue. Lymph nodes paradoxically maintain robust tissue architecture in homeostasis yet are continually poised for extensive tissue expansion upon immune challenge. We find that following immune challenge, cytoskeletal mechanics of a cellular meshwork of fibroblasts determine tissue tension independently of extracellular matrix scaffolds. We determine that CLEC-2/podoplanin signalling regulates the cell surface mechanics of fibroblasts, permitting cell elongation and interdigitation through expedited access to plasma membrane reservoirs. Increased tissue tension through the stromal meshwork gates the initiation of fibroblast proliferation, restoring homeostatic cellular ratios and tissue structure through expansion.

biophysics↗

bioRxiv2020

Junctional and cytoplasmatic contributions in wound healing

Wound healing is characterised by the re-epitheliation of a tissue through the activation of contractile forces concentrated mainly at the wound edge. While the formation of an actin purse string has been identified as one of the main mechanisms, far less is known about the effects of the viscoelastic properties of the surrounding cells, and the different contribution of the junctional and cytoplasmic contractilities. In this paper we simulate the wound healing process, resorting to a hybrid vertex model that includes cell boundary and cytoplasmatic contractilities explicitly, together with a differentiated viscoelastic rheology based on an adaptive rest-length. From experimental measurements of the recoil and closure phases of wounds in the Drosophila wing disc epithelium, we fit tissue viscoelastic properties. We then analyse in terms of closure rate and energy requirements the contributions of junctional and cytoplasmatic contractilities. Our results suggest that reduction of junctional stiffness rather than cytoplasmatic stiffness has a more pronounced effect on shortening closure times, and that intercalation rate has a minor effect on the stored energy, but contributes significantly to shortening the healing process, mostly in the later stages. Author summaryWe simulate the wound healing process of epithelia in the absence of substrate. By analysing the recoil process we are able to fit the viscoelastic properties of the monolayer, and study the influence of contractility at junctions and at the interior polymer network. We numerically simulate the whole wound opening and closure process, and inspect which mechanism has a more pronounced effect in terms of energy barrier and wound closure rate. We conclude that while junctional stiffness seems to be more effective than bulk stiffness at speeding up the closure, the increase of intercalation process is the mechanism with the lowest energy cost.

cell biology↗

bioRxiv2018

Tissue Fluidity Promotes Epithelial Wound Healing

Epithelial tissues are inevitably damaged from time to time and must therefore have robust repair mechanisms. The behaviour of tissues depends on their mechanical properties and those of the surrounding environment1. However, it remains poorly understood how tissue mechanics regulates wound healing, particularly in in vivo animal tissues. Here we show that by tuning epithelial cell junctional tension, we can alter the rate of wound healing. We observe cells moving past each other at the wound edge by intercalating, like molecules in a fluid, resulting in seamless wound closure. Using a computational model, we counterintuitively predict that an increase in tissue fluidity, via a reduction in junctional tension, can accelerate the rate of wound healing. This is contrary to previous evidence that actomyosin tensile structures are important for wound closure2-6. When we experimentally reduce tissue tension, cells intercalate faster and wounds close in less time. The role we describe for tissue fluidity in wound healing, in addition to its known roles in developing7,8 and mature tissues9, reinforces the importance of the fluid state of a tissue.

biophysics↗