In roughly one out of every 1,000 pregnancies, a structure no larger than a fingertip fails to snap shut at the right moment. The neural tube—the embryonic precursor to the brain and spinal cord—sometimes stays open, leading to conditions like spina bifida. Now, physicists at the Georgia Institute of Technology have helped explain why this critical closure happens the way it does, revealing the elegant physics that drive one of the body's earliest and most consequential transformations.
Working alongside researchers at University College London, the Georgia Tech team used computer models to show how, during the first weeks of development, living cells physically tug the neural tube closed—much like pulling a drawstring on a bag. Their findings, published in Current Biology, offer new insight into a process that, when disrupted, can result in severe birth defects.
"Understanding a complex developmental process like neural tube closure requires a highly interdisciplinary approach," said Shiladitya Banerjee, an associate professor in Georgia Tech's School of Physics. "By combining advanced biological imaging with theoretical physics, we were able to uncover the mechanical rules that drive cells to close the tube."
The research team, led in part by Gabriel Galea at UCL, studied mouse embryos—which develop remarkably similarly to human embryos—and fed that biological data into computational models. What emerged was a clear picture of the mechanism that enables neural tube closure: a so-called "purse string" made of actin, a protein that forms the scaffold inside every cell.
"These actin molecules are very important because they give rigidity and shape to cells," Banerjee explained. "During neural tube closure, actin filaments form a ring around the opening and engage molecular motors—proteins that generate forces inside cells. As these motors pull on the actin, they generate tension that tightens the ring and draws the tube closed."
As the actin ring cinches tighter, the surrounding cells stretch and elongate, aligning and moving together in a synchronized pattern. Banerjee describes this as akin to a school of fish responding as one—or a team tightening their grip on a shared rope. This coordination increases tension and drives a feedback loop that ultimately seals the neural tube.
The computational model the team built demonstrates how this feedback loop leads to successful neural tube formation. Moving forward, the researchers hope to use the same approach to understand why the process sometimes fails.
"Physics-based modeling of cell and tissue mechanics allows us to connect the dots between developmental stages in a way that is both robust and quantitative, simulating experiments that are impossible in biological tissues," said Galea. "In this case, it allowed us to explain how a cell's mechanical experience impacts its current and future shapes during a critical step of brain development."
Beyond neural tube development, the researchers say this interdisciplinary approach could be applied to other stages of human development where forces, motion, and timing are just as critical—potentially opening new avenues for understanding and ultimately preventing birth defects before they occur.