Vivek Malhotra was certain something was wrong with the microscope slides. When postdoctoral researcher Soumya Bhattacharyya first showed him the images in May 2024, the patterns were unmistakable—bright spherical structures inside human liver cells that shouldn't exist according to half a century of textbook knowledge. Those droplets would eventually upend what scientists thought they knew about collagen, the human body's most abundant protein.
For the last 50 years, cell biologists have puzzled over a seemingly impossible logistics problem. Collagen molecules, when viewed under a microscope, appear as rigid rods stretching up to 400 nanometers long. Yet the cellular transport vessels that ferry proteins out of cells are only 60 to 90 nanometers wide. How could something so large fit through something so small? The answer, published this year in the Journal of Cell Biology, is that the textbook picture was incomplete: inside living cells, collagen isn't a rigid rod at all.
Researchers at Barcelona's Center for Genomic Regulation discovered that collagen exists as a liquid-like droplet inside cells—a finding Malhotra describes as fundamentally shifting our understanding of the body's structural protein. "Inside a cell, collagens are not rigid molecules as one had assumed," explains Malhotra, the study's senior author. "They are in fact very pliable, taking a liquid condensate form much like oil in a drop of water."
The team studied procollagen 1, a precursor form that makes up roughly 90 percent of the body's total collagen, by observing human liver cells—the cells responsible for producing collagen and driving scarring in liver fibrosis. Using high-resolution live-cell imaging, they watched as collagen droplets merged, split, and exchanged material with their surroundings, unmistakable signatures of a condensate rather than a rigid structure. Bhattacharyya recalls the initial skepticism. "I thought it must be an artifact," Malhotra admits. Over subsequent months, the team had to verify that these weren't simply clumps of misfolded proteins destined for cellular disposal, but rather a natural, functional state.
The liquidlike form serves a critical protective purpose. Once collagen exits cells and assembles into rigid fibers, it becomes the structural scaffold holding tissues, bones, skin, and organs together. If collagen adopted that fibrous form while still inside the cell, it would likely be catastrophic. "If it were to become fibrous, it would kill the cell," Malhotra notes. The liquid state allows cells to safely house and transport the protein until the moment it needs to lock into its rigid, load-bearing form outside cellular boundaries.
This discovery has opened new questions about how cells actually move collagen from where it's made—the endoplasmic reticulum—to the cell's exterior. The researchers propose a "liquid extrusion" hypothesis, suggesting collagen moves through capillary action rather than via conventional vesicle transport, a mechanism long established since Nobel Prize-winning work in the 1980s and 1990s. That rethinking could reshape understanding of wound healing, fibrosis, and even cancer biology. What began as puzzlement over bright spots on a microscope slide may ultimately help scientists understand how the body's most abundant protein does the structural work that holds us together.