For more than a century, scientists assumed the thin extensions of brain cells that carry electrical signals, known as axons, were smooth, tube-shaped structures. A new study debunks that long-standing view of brain cell structure, showing that axons instead form a repeated pearl-like pattern under near-natural conditions. This shape directly controls how fast signals travel through the brain.
The findings, published in Nature Neuroscience, come from researchers at Johns Hopkins University School of Medicine. Lead author Jacqueline M. Griswold and her team discovered that unmyelinated axons carry repeated tiny swellings about 200 nanometers (0.0000079 inches) wide.
These swellings are connected by ultra-thin segments roughly 60 nanometers (0.0000024 inches) in diameter. The researchers called this pattern “nanopearling,” distinguishing it from the larger deformations seen in dying or degenerating neurons.
Johns Hopkins team uncovers the true shape of axons
The reason earlier studies missed this was the preservation method they used. Chemical-based fixation, the standard approach for decades, distorted fine membrane structures and made axons appear cylindrical. Griswold’s team used high-pressure freezing instead, a technique that preserves tissue in a near-natural state.
When applied to three different mouse brain preparations, including freshly extracted brain tissue, organotypic slice cultures, and dissociated hippocampal cultures, the pearl pattern appeared consistently across all of them. Live-cell imaging confirmed the pearls were stable, did not move or merge, and were not synapses.
To explain what drives this shape, the researchers built a computer model based on membrane physics. The model showed that the pearl pattern arises from the physical properties of the membrane itself, particularly its tension.
When the team exposed neurons to solutions of varying concentration, the pearl size changed exactly as the model predicted. Doubling the osmolarity shrank the swellings by 45 percent in width, while halving it caused them to expand by the same margin.
Scientists debunk 100-year-old brain cell structure theory
Cholesterol also played a central role. Removing it from the membrane using a compound called “MβCD” reduced pearl length and slowed electrical signal conduction velocity by about 28 percent.
Blocking a motor protein called nonmuscle myosin II widened the connector regions between pearls and increased conduction velocity by 19 percent. Disrupting the periodic actin ring structure of the axon, however, did not meaningfully alter the pearl shape.
This pointed to membrane mechanics, rather than the cytoskeleton, as the primary driver of the pearl shape.
The study also found that high-frequency electrical stimulation caused pearls to grow larger, with the width increasing by 17 percent. At the same time, membrane cholesterol dropped by about 45 percent. This structural change slowed signal conduction velocity and persisted for at least 60 minutes after stimulation.
When researchers artificially depleted cholesterol before stimulation, structural changes still occurred, but conduction velocity no longer slowed. This suggested cholesterol movement is specifically needed to trigger that functional shift.
Cholesterol mobilization triggers changes in signal conduction speed
Griswold and her colleagues also noted that this pearl-like morphology appears in neurons of simpler organisms, including roundworms and comb jellies. This suggests it is an ancient and conserved feature of nerve cells rather than something unique to mammals.
Researchers say the findings reframe how the brain encodes and transmits information, showing that the physical shape of axons is actively tuned by the cell’s own membrane chemistry.
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