Changes in collagen organization, chirality predate visible damage

Ali Haider, a graduate student at HU and WPI-SKCM2 and first author of the study, observes the skin structure using confocal microscopy to investigate collagen organization and extracellular matrix remodelling. Photo by Ali Haider / Hiroshima University

An international team led by researchers at Hiroshima University has developed a new way to detect subtle, early-stage changes in human skin collagen before any visible signs of damage appear. In the study, published in ACS Nano on July 16, 2026, the investigators report that the molecular organization and supramolecular chirality of dermal collagen collapse before the actual thinning or fragmentation of the visible fibre network.

In a press release from the university, the researchers note that traditional skin imaging methods can easily identify visible deterioration of the collagen network, such as fibre thinning or loss of connectivity. However, these structural failures represent late stages of tissue remodelling.

“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, in the release. “It’s similar to detecting changes in the arrangement of words and sentences in a book before any pages appear damaged or missing.”

Haider is a graduate research fellow at Hiroshima University’s International Institute for Sustainability with Knotted Chiral Meta Matter (WPI-SKCM²).

To uncover these hidden patterns, the team integrated advanced optical imaging with chiroptical spectroscopy, including synchrotron radiation vacuum-ultraviolet circular dichroism (SR-VUVCD) and multi-dimensional quantum cascade laser vibrational circular dichroism (MultiD-QCL-VCD). This framework allowed them to map both the presence of collagen and its chiral structural coherence in the same physical tissue section.

The results demonstrated a distinct decoupling between collagen mass and structural order. They found tissue samples retained their bulk collagen content and coverage even after their underlying supramolecular chirality coherence had severely degraded.

“The key message of this paper is that collagen should not be viewed only as a visible fibre 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.”

The researchers’ goal is to establish a comprehensive framework that integrates molecular chirality, supramolecular organization, and macroscopic tissue architecture. This could provide insights for medical interventions, wound healing, and biomaterial design, allowing researchers to evaluate tissue integrity before irreversible macroscopic breakdown occurs.