Active Cells, Biochemistry & Physiology Bones, Joints & Muscles

Multi-tissue mechanics in the development and engineering of the posterior body axis

Funder Wellcome Charity-funded
Recipient organisation University of Cambridge
Funding £2.1M
Period Jan 2023 — Jan 2031

In plain English

AI plain-English summary

A zebrafish embryo elongates its body by coordinating the mechanical forces between its spinal cord, notochord, and muscle precursors—and researchers want to know exactly how those tissues push and pull on each other to get the proportions right. This matters because current lab-grown organoids—tiny clusters of cells meant to mimic real organs—often develop abnormal shapes. Without understanding the mechanical interplay between tissues, scientists cannot engineer organoids that faithfully replicate human development. The problem is especially clear in the posterior body axis, where three different tissues must elongate in sync. The team will first disrupt the spinal cord and notochord in zebrafish embryos and measure how that changes the forces on the adjacent muscle-forming tissue. Then they will build mouse stem-cell aggregates—gastruloids—and test how varying the stiffness and composition of the surrounding gel affects cell behaviour. Finally, they will physically compress these gastruloids using micro-cantilevers to recreate the forces an embryo experiences. This is fundamental developmental biology with a direct engineering payoff. Success would give bioengineers a recipe for building organoids with realistic anatomy, improving their use in drug screening and disease modelling.

View original technical description
During development tissues wrapped in extra-cellular matrix (ECM) undergo well-defined deformations to build an embryo. How morphogenetic provides mechanical forces to control the shaping of adjacent tissues is unknown. However, a clear understanding of multi-tissue mechanics is essential to engineer the morphogenesis of organoids in vitro if we wish to use these structures to accurately model their in vivo counterparts. Vertebrate posterior body elongation exemplifies the problem of multi-tissue morphogenesis as the shaping of the notochord, spinal cord and somitic mesoderm must be coordinated together generate a proportioned body axis. We will measure how mechanical forces impacting upon the zebrafish pre-somitic mesoderm alter when spinal cord and notochord expansion is disrupted and characterize the impact on tissue elongation and signalling. A second aim will model pre-somitic mesoderm elongation in aggregates of mouse embryonic stem cells or gastruloids. By modulating the stiffness and ECM composition surrounding the organoid, we will assess their impact on mesoderm progenitor self-renewal. Finally, we will recapitulate in vivo multi-tissue mechanics by encapsulating gastruloids in matrix and applying compressive forces using micro-cantilevers and microfluidics. It will enable a reciprocal interaction between developmental biology and bioengineering in developing new approaches to engineer improved morphology of multicellular systems.

View the original record at the funder ↗

Researchers

Benjamin Steventon (EPMC Awardee)

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Original classification

Discovery Award

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.