Scientists have identified early signs of skin aging, finding that collagen’s internal structure begins to unravel before the fibers themselves break apart.
Skin can appear structurally intact even as the collagen beneath it begins losing its internal organization. An international research team led by Hiroshima University has developed a method for detecting these early changes before conventional imaging reveals visible damage. Published July 16, 2026, in ACS Nano, the study found that the molecular arrangement and supramolecular chirality—or structural handedness—of dermal collagen deteriorate before its fiber network begins to thin or fragment.
Collagen supports the skin through a carefully organized hierarchy that extends from molecules to larger fibers. This arrangement gives tissue much of its structure and mechanical strength. Standard imaging can reveal advanced deterioration, including thinning fibers and broken connections, but those visible changes appear relatively late in the remodeling process.
“One way to think about our findings is that conventional imaging methods can show the ‘bricks’ of a collagen structure, but they may miss subtle changes in how those bricks are arranged,” said Ali Haider, first author of the study and a graduate research fellow at Hiroshima University’s International Institute for Sustainability with Knotted Chiral Meta Matter (WPI-SKCM2). “It’s similar to detecting changes in the arrangement of words and sentences in a book before any pages appear damaged or missing.”
New tools expose hidden collagen changes
To identify changes that ordinary imaging could not detect, the researchers combined advanced optical imaging with chiroptical spectroscopy, a method that measures how structures with a particular handedness interact with light. Their approach included synchrotron radiation vacuum-ultraviolet circular dichroism (SR-VUVCD) and multi-dimensional quantum cascade laser vibrational circular dichroism (MultiD-QCL-VCD).
Using these complementary techniques, the researchers examined collagen abundance and the coherence of its chiral organization within the same physical section of tissue. This direct comparison allowed them to distinguish between the amount of collagen present and the condition of its underlying molecular structure.
Structural order fails before fibers disappear
The measurements revealed that collagen quantity and collagen organization do not necessarily decline together. Tissue samples could retain much of their overall collagen coverage and mass even after the coherence of their supramolecular chirality had deteriorated substantially.
In other words, the visible fiber network could still appear largely intact while its internal order was already breaking down. That separation suggests that collagen deterioration begins at smaller structural scales before becoming obvious through changes in fiber shape or abundance.
“The key message of this paper is that collagen should not be viewed only as a visible fiber network but as a hierarchical material whose function depends on organization across multiple length scales,” said Katsuya Inoue, a professor at WPI-SKCM2 who is one of the study’s corresponding authors. “Our study shows that advanced correlative methods can reveal changes in this hidden organization that are not apparent from morphology alone.”
Earlier detection could improve tissue assessment
The researchers ultimately hope to create a broader framework connecting molecular chirality, supramolecular organization and the large-scale architecture of tissue. By measuring all three levels together, researchers may be able to assess tissue integrity before damage becomes irreversible and visible.
Such an approach could provide useful information for wound healing research, biomaterial development and future medical interventions. Rather than waiting for collagen fibers to thin or break apart, researchers could potentially identify the earlier loss of structural organization that precedes those changes.
Reference: “Correlative Multimodal Framework Reveals Supramolecular Chirality Loss Preceding Fibrillar Rarefaction in Dermal Collagen” by Ali Haider, Yusuke Kochi, Andrew K. Schulz, Kuya Aoyama, Aiko Sada, Hisako Sato, Elisabeth Matsumoto, Malcolm Kadowdwala, Koichi Matsuo and Katsuya Inoue, July 16, 2026, ACS Nano.
DOI: 10.1021/acsnano.6c06602
This work was supported by WPI-SKCM2, Institut Henri Poincaré, LabEx CARMIN, and the Alexander von Humboldt Foundation.
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