An international research team led by Hiroshima University has developed a technique that can reveal very early changes in collagen in human skin, long before the damage is visible with conventional imaging.
The survey results are ACS nano Jul 16, 2026 Researchers suggest that collagen begins to lose its precise molecular organization before the fibers become thinner, fragmented, or cut. In other words, the skin tissue may appear structurally intact even after important changes have already begun at deep levels.
Hidden damage within skin collagen
Collagen is the main structural protein of the skin. They form complex networks that help maintain tissue strength, flexibility, and resistance to physical stress.
Its structure is organized across multiple scales. Individual molecules come together into large bundles to form the fibers that support the skin. Because of this layered arrangement, collagen is described as a hierarchical substance.
Most traditional imaging methods focus on the visible features of that network. Detect fibers that are thinned, broken apart, or have lost connections. However, these changes tend to appear relatively late in the remodeling process.
New research shows that collagen can lose its underlying structural order, even though the visible fibrous network still appears largely unchanged.
“One way to think about our findings is that traditional imaging methods can show the ‘bricks’ of collagen structure, but may miss subtle changes in how those bricks are arranged,” said Ali Haider, lead author of the study and a graduate researcher at Hiroshima University’s International Institute for Sustainability (WPI-SKCM2). “This is similar to detecting changes in the arrangement of words and sentences in a book before pages become damaged or missing.”
Detection of collagen structural handedness
To identify these hidden changes, the researchers combined advanced optical imaging with chiroptical spectroscopy.
Chiropractic techniques examine how molecules interact with polarized light. These are particularly useful for studying chirality, sometimes described as structural handedness. Many biological structures have a preferred orientation, just as the human left and right hands mirror each other but cannot be perfectly superimposed.
Collagen has this kind of organized handedness, both at the molecular level and at the larger structural level. As the tissue begins to deteriorate, it can lose important functional properties, even if the total amount of collagen remains unchanged.
The research team used synchrotron 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 consistency within the same section of tissue.
Collagen can remain even when order disappears
The analysis revealed a clear distinction between the amount of collagen and its tissue quality.
Tissue samples maintained most of their total collagen content and surface coverage even after the supramolecular chirality consistency was significantly reduced. This means that measuring only the amount of collagen present may provide an incomplete picture of tissue health.
Even though the internal structure of the protein is already disintegrating, the sample may still contain abundant collagen.
“The key message of this paper is that we should view collagen not only as a visible fibrous network, but also as a hierarchical material whose function depends on organization across multiple length scales,” said WPI-SKCM2 Professor Katsuya Inoue, one of the study’s corresponding authors. “Our study shows that advanced correlational techniques can reveal changes in this hidden tissue that are not obvious from morphology alone.”
Early clues to tissue deterioration
Ultimately, the researchers hope to build a broader framework that connects molecular chirality, supramolecular organization, and the large-scale structure of tissues.
Such a system could help scientists assess tissue integrity before major structural damage becomes irreversible. It also has the potential to provide new insights into wound healing, medical procedures, and the design of biomaterials that mimic or interact with living tissues.
Rather than waiting until collagen fibers become visibly thinner or fragmented, future researchers may be able to identify early warning signs by looking at how the molecules are arranged.
international research cooperation
The research was conducted by Ali Haider, Yusuke Kochi, Andrew K. Schultz, Kuya Aoyama, Aiko Sada, Hisako Sato, Elisabetta Matsumoto, Malcolm Kaddwala, Koichi Matsuo, and Katsuya Inoue.
The researchers are representatives from Hiroshima University (including WPI-SKCM², the Graduate School of Advanced Science and Engineering, the Chirality Research Center, and the 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 experts from Japan, Germany, the United States, and the United Kingdom.
This research was supported by WPI-SKCM2, the Henri Poincaré Institute, LabEx CARMIN, and the Alexander von Humboldt Foundation.
