UCL scientists have successfully embedded mechanical force sensors directly into the developing brains and spinal cords of chick embryos, which they hope will improve understanding and prevention of birth defects such as spina bifida.
The study, published in Materials from nature and in collaboration with the University of Padua and the Institute of Molecular Medicine of Veneto (VIMM), uses innovative biotechnologies to measure the mechanical forces exerted by the embryo during its development.
These forces are crucial in the formation of organs and anatomical systems, such as the formation of the neural tube, which gives rise to the central nervous system.
Congenital malformations of the spinal cord affect approximately one in every 2,000 newborns in Europe each year.
Although these malformations have been studied for decades, they cannot be fully explained solely by molecular and genetic studies.
As a result, researchers are now studying the physical and mechanical forces on tissues during embryo development. However, this can be challenging as the embryonic spinal cord is tiny (too small to be seen with the naked eye) and extremely delicate. Therefore, force-measuring devices must be equally small and gentle so as not to disrupt normal growth.
To overcome these difficulties, the researchers 3D printed tiny force sensors (about 0.1 mm wide) directly inside the developing nervous system of chicken embryos.
These force sensors start out as a liquid that is applied directly to developing embryos. When exposed to a powerful laser, the liquid transforms into a spring-like solid. This solid attaches to the embryos’ growing spinal cord and is deformed by the mechanical forces produced by the embryo’s cells.
This allowed them to measure the tiny forces (about a tenth of the weight of a human eyelash) that embryos must generate to form the spinal cord.
For normal embryonic development, these forces must be greater than the opposing negative forces.
Quantifying the forces would allow researchers to explore drugs that could sufficiently increase positive forces or decrease negative forces to help prevent birth defects such as spina bifida.
These medications may also complement the benefits of folic acid intake, a well-established strategy for preventing developmental problems before and during pregnancy.
Lead author, Marie Sklowdowska Curie postdoctoral fellow Dr Eirini Maniou (UCL Great Ormond Street Institute of Child Health and University of Padua), said: “Through the use of new biomaterials and advanced microscopy, this study promises a step-change in the field of embryonic mechanics and lays the foundation for a unified understanding of development.
“Our work paves the way for identifying new preventive and therapeutic strategies for central nervous system malformations.”
The research group also demonstrated that the same technology could be applied to human stem cells as they develop into bone marrow cells.
In the future, this could allow comparisons between stem cells from healthy donors and those from spina bifida patients, with the aim of understanding why some people develop the disease.
Co-lead author Dr Gabriel Galea (UCL Great Ormond Street Institute of Child Health) said: “This technology is highly versatile and widely applicable to many fields of research, and we hope it will be rapidly adopted and applied by other groups to address fundamental questions.”
Co-senior author Professor Nicola Elvassore (University of Padua and VIMM) added: “This discovery not only allows us to better understand the mechanical forces involved during embryonic development, but also offers new insights into intervening and preventing conditions such as spina bifida.
“The ability to quantify embryonic forces with such precision represents a significant advance in biomedical research.”