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

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.

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.

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.

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."

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.