Collagen is often described as the body’s natural scaffolding. It gives strength and structure to skin, bones, tendons, organs, and many other tissues.
For decades, biology textbooks have shown collagen as a long, stiff, rod-shaped molecule. But a surprising new study suggests that picture is only part of the story.
Researchers at the Center for Genomic Regulation (CRG) in Barcelona have discovered that collagen behaves very differently inside living cells.
Instead of existing as a rigid rod, collagen forms tiny liquid-like droplets that resemble oil floating in water.
The findings, published in the Journal of Cell Biology, provide the first direct view of how collagen naturally exists inside cells before it is released into the body.
Collagen is the most abundant protein in humans, accounting for roughly one-third of the body’s total protein. The researchers believe its liquid-like form may serve an important protective role.
Outside cells, collagen assembles into strong fibers that help hold tissues together. However, if those same fibers formed inside a cell, they could cause serious damage.
According to senior author Professor Vivek Malhotra, the liquid state may prevent collagen from becoming fibrous too early. If collagen formed rigid fibers inside the cell, it could interfere with normal cellular functions and potentially kill the cell.
The discovery may also help solve a long-standing mystery in biology. Collagen is produced inside a structure called the endoplasmic reticulum, or ER. Scientists have struggled for decades to understand how collagen leaves this compartment and is transported out of the cell.
The problem is one of size. Mature collagen molecules can be up to 400 nanometers long, while the tiny sacs, known as vesicles, that normally transport proteins are only about 60 to 90 nanometers wide. It has never been clear how such a large molecule could fit inside these transport containers.
The new study suggests that collagen may not be transported in the traditional way at all.
Using advanced live-cell imaging, researchers observed collagen inside human liver cells that produce large amounts of the protein. They found that collagen gathered into tiny droplets that merged, split apart, and exchanged material with their surroundings. These behaviors are characteristic of structures known as condensates, which are liquid-like compartments formed when proteins become highly concentrated.
The discovery was unexpected. When the researchers first saw the bright spherical droplets under the microscope, they suspected they might simply be clumps of damaged proteins. However, further testing showed the droplets contained properly folded collagen and helper proteins that support normal collagen production.
The study also sheds light on the role of a protein called TANGO1, which is known to be essential for collagen export. Researchers found that collagen droplets still formed when TANGO1 was removed, but they were no longer positioned correctly at the cell’s export sites. As a result, collagen secretion dropped significantly.
The team now proposes a new “liquid extrusion” model in which collagen droplets flow through cellular exit points much like liquid moving through a narrow tube.
If future studies confirm this mechanism, the discovery could have important medical implications. Excess collagen production contributes to diseases such as liver, lung, and skin fibrosis, where scar tissue builds up and damages organs. Collagen also helps create protective barriers around tumors, making some cancers harder to treat.
By better understanding how collagen leaves cells, scientists may eventually develop new ways to reduce harmful scar tissue or break down the collagen-rich shields that help tumors evade chemotherapy and the immune system.
What began as an unexpected observation under a microscope could ultimately lead to new strategies for treating some of the most challenging diseases.
