The mystery of human wrinkles: What do the cells say?

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A research team consisting of Professor Dong Sung Kim, Professor Anna Lee, and Dr. Jaeseung Youn from the Department of Mechanical Engineering at POSTECH has successfully recreated the structure of wrinkles in biological tissue in vitro, uncovering the mechanisms behind their formation. Their findings were published on August 19 within the international journal Nature Communications.

While wrinkles are sometimes related to skin aging, many organs and tissues, including the brain, stomach, and intestines, even have distinct wrinkle patterns. These structures play a key role in regulating cellular states and differentiation, contributing to the physiological functions of every organ. Understanding how biological tissues fold and form wrinkles is significant for understanding the complexity of living organisms beyond cosmetic concerns. This information might be central to advancing research in areas equivalent to skin aging, regenerative therapies, and embryology.

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

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 tool able to applying precise compressive forces, they successfully recreated and observed wrinkle structures in vitro which might be typically seen within the gut, skin, and other tissues in vivo. This breakthrough allowed them, for the primary time, to copy each the hierarchical deformation of a single deep wrinkle brought on by a robust compressive force and the formation of diverse small wrinkles under lighter compression.

The team also discovered that aspects equivalent to 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 inside the ECM layer, leading to the formation of wrinkles. Moreover, they found that dehydration of the ECM layer was a key consider the wrinkle formation process. These observations closely mirrored the results seen in aging skin where dehydration of the underlying tissue layer results in wrinkle development, providing a mechanobiological model for understanding wrinkle formation.

Professor Dong Sung Kim expressed the importance of the research by saying, “We now have developed a platform that may replicate various wrinkle structures in living tissue without the necessity for animal testing.” He added, “This platform enables real-time imaging and detailed remark of cellular and tissue-level wrinkle formation, processes which might be difficult to capture in traditional animal models. It has wide-ranging applications in fields equivalent to embryology, biomedical engineering, cosmetics, and more.”

The research was conducted with support from the Mid-Profession 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.

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