An international research team led by Hiroshima University has developed a technique that can reveal extremely early changes in human skin collagen, long before damage becomes visible with conventional imaging.
The findings, published in ACS Nano on July 16, 2026, suggest that collagen begins to lose its precise molecular organization before its fibers become thinner, fragmented, or disconnected. In other words, skin tissue may appear structurally intact even after major changes at a deeper level have already begun.
Hidden damage within the skin’s collagen
Collagen is the main structural protein of the skin. It forms an intricate network that helps tissues remain strong, flexible and resistant to physical stress.
Its structure is organized on several scales. The individual molecules assemble into larger bundles, which then form the fibers that support the skin. Because of this layered arrangement, collagen is described as a hierarchical material.
Most traditional imaging methods focus on the visible features of that network. They can detect fibers that have thinned, broken, or lost their connections. However, those changes tend to appear relatively late in the remodeling process.
The new research indicates that collagen can lose its underlying structural order while the visible fiber network still appears virtually unchanged.
“One way to think about our findings is that conventional imaging methods may show the ‘bricks’ of a collagen structure, but may miss subtle changes in the way those bricks are arranged,” said Ali Haider, first author of the study and a graduate researcher at Hiroshima University’s International Institute for Sustainability with Knotted Chiral Metamatter (WPI-SKCM).2). “It’s similar to detecting changes in the arrangement of words and sentences in a book before any pages appear damaged or missing.”
Detection of structural laterality of collagen
To identify these hidden changes, the researchers combined advanced optical imaging with chiroptic spectroscopy.
Chiroptical methods examine how molecules interact with polarized light. They are especially useful for studying chirality, a property sometimes described as structural laterality. Just as a person’s left and right hands mirror each other but cannot overlap perfectly, many biological structures have a preferred orientation.
Collagen has this type of organized laterality at both a molecular and broader structural level. When that organization begins to deteriorate, the tissue can lose important functional properties even if its total amount of collagen remains unchanged.
The team used synchrotron radiation vacuum ultraviolet circular dichroism (SR-VUVCD) and multidimensional quantum cascade laser vibrational circular dichroism (MultiD-QCL-VCD). By combining these methods with imaging, the researchers were able to measure collagen abundance and structural coherence within the same tissue section.
Collagen can remain while its order disappears
The analysis revealed a clear separation between the quantity of collagen and the quality of its organization.
The tissue samples maintained much of their total collagen content and surface coverage, even after the coherence of their supramolecular chirality had substantially deteriorated. This means that measuring only the amount of collagen present may provide an incomplete picture of tissue health.
A sample may still contain abundant collagen while the internal architecture of the protein is already breaking down.
“The key message of this paper is that collagen should not be viewed only as a network of visible fibers, but as a hierarchical material whose function depends on organization at multiple length scales,” said Katsuya Inoue, professor at WPI-SKCM.2 who is one of the corresponding authors of the study. “Our study shows that advanced correlative methods can reveal changes in this hidden organization that are not evident from morphology alone.”
Previous Clues to Tissue Deterioration
Ultimately, the researchers hope to build a broader framework that connects molecular chirality, supramolecular organization, and large-scale tissue architecture.
Such a system could help scientists assess tissue integrity before major structural damage becomes irreversible. It may also offer new insights into wound healing, medical treatments, and the design of biomaterials that mimic or interact with biological tissue.
Instead of waiting until collagen fibers visibly thin or fragment, future researchers could identify early warning signs by examining how the molecules are arranged.
An international research collaboration
The study was conducted by Ali Haider, Yusuke Kochi, Andrew K. Schulz, Kuya Aoyama, Aiko Sada, Hisako Sato, Elisabetta Matsumoto, Malcolm Kadodwala, Koichi Matsuo and Katsuya Inoue.
The researchers represent Hiroshima University (including WPI-SKCM², the Graduate School of Advanced Science and Engineering, the Chirality Research Center, and the Research Institute for Synchrotron Radiation Science), the Max Planck Institute for Intelligent Systems, Kyushu University, Kumamoto University, Ehime University, Georgia Institute of Technology, and the University of Glasgow.
The collaboration brought together specialists from Japan, Germany, the United States and the United Kingdom.
This work was supported by WPI-SKCM2Institut Henri Poincaré, LabEx CARMIN and the Alexander von Humboldt Foundation.