The Mystery of Human Wrinkles: Scientists Unveil Secret Mechanisms

Wrinkled Skin
A research team replicated biological wrinkle structures in vitro, identifying factors like compressive force and dehydration as key. Their research could advance skin aging studies and regenerative therapies.

A POSTECH research team has recreated biological wrinkles in vitro, revealing that ECM dehydration and compressive forces are crucial in wrinkle formation. This platform offers real-time imaging and broad applications in biomedical and cosmetic research.

A research team from POSTECH’s Department of Mechanical Engineering, led by Professor Dong Sung Kim, Professor Anna Lee, and Dr. Jaeseung Youn, has successfully replicated the structure of wrinkles in biological tissue in vitro, shedding light on the mechanisms driving their formation. Their findings were published in the journal Nature Communications on August 19.

While wrinkles are often associated with skin aging, many organs and tissues, including the brain, stomach, and intestines, also have distinct wrinkle patterns. These structures play a key role in regulating cellular states and differentiation, contributing to the physiological functions of each organ. Understanding how biological tissues fold and form wrinkles is vital for understanding the complexity of living organisms beyond cosmetic concerns. This knowledge can be central to advancing research in areas such as skin aging, regenerative therapies, and embryology.

Challenges in Wrinkle Formation Research

Despite the significance of biological wrinkle structures, much of the research in this area has relied on animal models including fruit flies, mice, and chickens, due to limitations in replicating wrinkle formation in vitro. As a result, the detailed processes behind wrinkle formation in living tissue remain largely unknown.

Wrinkled Epithelium Hydrogel
Image of wrinkled epithelium on the ECM hydrogel layer in response to compression. Credit: POSTECH

Professor Dong Sung Kim’s team addressed this limitation by developing an epithelial tissue model composed solely of human epithelial cells and extracellular matrix (ECM). By combining this model with a device capable of applying precise compressive forces, they successfully recreated and observed wrinkle structures in vitro that are typically seen in the gut, skin, and other tissues in vivo. This breakthrough allowed them, for the first time, to replicate both the hierarchical deformation of a single deep wrinkle caused by a strong compressive force and the formation of numerous small wrinkles under lighter compression.

Key Factors in Wrinkle Formation

The team also discovered that factors such as the porous structure of the underlying ECM, dehydration, and the compressive force applied to the epithelial layer are crucial to the wrinkle formation process. Their experiments revealed that compressive forces deforming the epithelial cell layer caused mechanical instability within the ECM layer, resulting in the formation of wrinkles. Additionally, they found that dehydration of the ECM layer was a key factor in the wrinkle formation process. These observations closely mirrored the effects seen in aging skin where dehydration of the underlying tissue layer leads to wrinkle development, providing a mechanobiological model for understanding wrinkle formation.

Professor Dong Sung Kim expressed the significance of the research by saying, “We have developed a platform that can replicate various wrinkle structures in living tissue without the need for animal testing.” He added, “This platform enables real-time imaging and detailed observation of cellular and tissue-level wrinkle formation, processes that are difficult to capture in traditional animal models. It has wide-ranging applications in fields such as embryology, biomedical engineering, cosmetics, and more.”

Reference: “Tissue-scale in vitro epithelial wrinkling and wrinkle-to-fold transition” by Jaeseung Youn, Dohui Kim, Hyunsu Kwak, Anna Lee and Dong Sung Kim, 19 August 2024, Nature Communications.
DOI: 10.1038/s41467-024-51437-z

The research was conducted with support from the Mid-Career Research Program of the National Research Foundation of Korea and the Ministry of Science and ICT, and the Alchemist Project of the Ministry of Trade, Industry and Energy.