An actin-based viscoplastic lock ensures progressive body-axis elongation

International audienceBody-axis elongation constitutes a key step in animal development, laying out the final form of the entire animal. It relies on the interplay between intrinsic forces generated by molecular motors1,2,3, extrinsic forces exerted by adjacent cells4,5,6,7 and mechanical resistance forces due to tissue elasticity or friction8,9,10. Understanding how mechanical forces influence morphogenesis at the cellular and molecular level remains a challenge1. Recent work has outlined how small incremental steps power cell-autonomous epithelial shape changes1,2,3, which suggests the existence of specific mechanisms that stabilize cell shapes and counteract cell elasticity. Beyond the twofold stage, embryonic elongation in Caenorhabditis elegans is dependent on both muscle activity7 and the epidermis; the tension generated by muscle activity triggers a mechanotransduction pathway in the epidermis that promotes axis elongation7. Here we identify a network that stabilizes cell shapes in C. elegans embryos at a stage that involves non-autonomous mechanical interactions between epithelia and contractile cells. We searched for factors genetically or molecularly interacting with the p21-activating kinase homologue PAK-1 and acting in this pathway, thereby identifying the α-spectrin SPC-1. Combined absence of PAK-1 and SPC-1 induced complete axis retraction, owing to defective epidermal actin stress fibre. Modelling predicts that a mechanical viscoplastic deformation process can account for embryo shape stabilization. Molecular analysis suggests that the cellular basis for viscoplasticity originates from progressive shortening of epidermal microfilaments that are induced by muscle contractions relayed by actin-severing proteins and from formin homology 2 domain-containing protein 1 (FHOD-1) formin bundling. Our work thus identifies an essential molecular lock acting in a developmental ratchet-like process

The stiffness of living tissues and its implications for tissue engineering

The past 20 years have witnessed ever- growing evidence that the mechanical properties of biological tissues, from nanoscale to macroscale dimensions, are fundamental for cellular behaviour and consequent tissue functionality. This knowledge, combined with previously known biochemical cues, has greatly advanced the field of biomaterial development, tissue engineering and regenerative medicine. It is now established that approaches to engineer biological tissues must integrate and approximate the mechanics, both static and dynamic, of native tissues. Nevertheless, the literature on the mechanical properties of biological tissues differs greatly in methodology, and the available data are widely dispersed. This Review gathers together the most important data on the stiffness of living tissues and discusses the intricacies of tissue stiffness from a materials perspective, highlighting the main challenges associated with engineering lifelike tissues and proposing a unified view of this as yet unreported topic. Emerging advances that might pave the way for the next decadeâ s take on bioengineered tissue stiffness are also presented, and differences and similarities between tissues in health and disease are discussed, along with various techniques for characterizing tissue stiffness at various dimensions from individual cells to organs.The authors would like to acknowledge financial support from the European Research Council, grant agreement ERC-2012-ADG 20120216-321266 (project ComplexiTE). C.F.G. acknowledges scholarship grant no. PD/BD/135253/2017 from Fundação para a Ciência e Tecnologia (FCT). The authors also thank the peer-reviewers for the constructive comments and suggestions that helped to shape this manuscript