Active Cells, Biochemistry & Physiology Heart, Stroke & Blood

Investigating the mechanosensitive interplays between genetic control and self-organisation during the emergence of cardiac tissue curvature

In plain English

AI plain-English summary

The developing heart bends itself into shape, and this project will investigate how mechanical forces—not just genetic instructions—guide that process. Congenital heart malformations account for up to 30% of embryos or foetuses lost before birth. Most research focuses on the genetic programmes that assign cell identities, but far less is known about the mechanical forces that physically assemble the growing heart. Abnormal forces can deregulate gene expression and cause congenital heart disease or cardiomyopathies. This project will explore how mechanotransduction—the process by which cells sense and respond to physical forces—coordinates genetic control with self-organisation during cardiac chamber formation. This is fundamental science. It will not produce a new drug or device in the short term. But understanding how mechanical cues shape a developing organ could eventually inform tissue engineering, improve the design of lab-grown heart tissue for transplantation, or help identify why certain pregnancies are at risk of cardiac defects. Similar fundamental work on mechanobiology has already changed how researchers think about cancer metastasis and wound healing.

View original technical description
Cardiovascular Diseases (CVDs) are the leading causes of death in the world. Congenital heart malformations account for as many as 30% of embryos or foetuses lost before birth. To properly develop, the heart needs to generate mechanical forces during the growth of the whole structure. This, in combination with genetic information, is required for assembling a functional heart. Currently, most studies focus on how genetic programmes control cell identities and their subsequent roles in cardiac development. In contrast, the mechanical forces that are integral to the growth and assembly of the heart are much less explored. This is surprising as abnormal mechanical forces can deregulate gene expression and lead to diseases such as congenital heart disease and cardiomyopathies. Understanding how biomechanics regulates cardiac morphogenesis is thus of utmost importance. This project will explore the interplay between genetic control and self-organization emerging from cell mechanics during cardiogenesis. Our hypothesis is that mechanotransduction is at the centre of this interplay. We will study the role of mechanotransduction in the emergence of multicellular flow and the mechanism of a newly characterized cell shape change associated with cardiac chamber morphogenesis.

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Researchers

Choon Hwai Yap (Co-Investigator)Julien Vermot (Principal Investigator)Molly Stevens (Co-Investigator)

Related Research

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Geometric and topological control of organogenesis

Original classification

Research Grant

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