Image: MPI for Biochemistry

Research that’s more than skin deep

Being the largest organ of the human body, the skin has numerous functions: It forms a barrier that prevents the body from drying out and protects it from injury and pathogen invasion. At the same time, it has to withstand continuous wear and tear. Three research groups funded by the Max and Ingeburg Herz Foundation are carrying out scientific research into the skin.

The skin forms the largest organ in the body. Among its many functions: protective shield, a store for nutrients and water, an excretory organ for metabolic breakdown products, absorbs medications, and a sensory organ. Idioms such as "to get under someone’s skin" and "I nearly jumped out of my skin" reflect the importance of the skin.

Molecular mechanotransduction: strong forces in cells

The Finnish researcher Sara Wickström, already distinguished for her work as a PhD candidate, was appointed head of the first Paul Gerson Unna Research Group at the Max Planck Institute for Biology of Ageing in 2010. Her team is studying molecular processes that enable the skin to serve as a barrier between the body and the outside world.

A highly complex system is required to regulate the various skin cell types and their interactions in order to maintain a balance between the self-renewal and differentiation, i.e. cell specialization, of this tissue, which has to withstand harsh environmental factors. If this balance is disturbed, the skin undergoes changes. The skin also ages so that it is no longer able to regenerate easily and wounds heal less quickly. Benign changes sometimes occur (psoriasis, eczema), but they can also degenerate into epidermal tumours (skin cancer), the most prevalent type of cancer in Europe. What are the basic principles of this cellular network that maintains the skin as a robust but continuously self-regenerating organ? How are the biomechanical properties of the cellular network that makes up the skin – e.g. cell density, packing, shape and contractility – converted into biochemical signals? The answers to these questions will create the basis for the development of treatments for ageing and other skin changes and allow people to remain healthier into old age.

Molecular mechanotransduction: strong forces in cells

Carsten Grashoff is studying the keratin-synthesizing cells of the epidermis to learn how forces are transferred within living cells. The cells of our body are exposed to a variety of physical forces: they are constantly compressed, sheared and stretched and react accordingly. However, it remains unclear exactly how mechanical forces are processed, as it is very difficult to measure forces in cells. Grashoff and his Research Group at the Max Planck Institute of Biochemistry are therefore developing microscopic methods that allow them to determine exactly where and when forces act on individual protein molecules in cells.

As a tool, they use elastic proteins such as the spider silk protein flagelliform, which can be stretched by tiny forces. The researchers combine the properties of such elastic proteins with a physical effect known as Förster Resonance Energy Transfer (FRET). FRET, which can occur between two dissimilar fluorescent molecules, varies with the distance between the two molecules. If the two fluorophores are linked to an elastic protein that stretches under force so that the distance between the fluorescent proteins increases, the mechanical force can be determined by measuring the FRET effect. Using the adhesion protein vinculin as an example, the researchers were able to show that their method works. Vinculin is located within the cell membrane and is required for cellular motility. This method allows the scientists to distinguish regions of high force from regions of low force. Such experiments make it possible to investigate the mechanisms underlying the transfer of energy in living cells in greater detail.

Explaining skin ageing with dermatogenomics

Another Paul Gerson Unna Research Group located at the MPG Partner Institute for Computational Biology in Shanghai (MPG-CAS). Under the direction of Sijia Wang, who won prestigious awards at a young age, the team is investigating the biology of the skin, hair and nails from a molecular genetic point of view. Dermatogenomics is the key field in the quest to explain the characteristics of the skin. To this end, large volumes of data are being collected, analyzed and compared both in China and in cooperation with partners in Western Europe to create a sort of world map showing the distribution of skin gene variants.

Skin characteristics – the most obvious one being pigmentation – display a broad range of variation. Moreover, individuals and ethnic groups differ in their skin responses to environmental factors such as strong solar radiation, cigarette smoke and, last but not least, exhaust emissions from industry and vehicles. The biological mechanisms underlying these differences are complex. Wang’s Research Group suspects that specific genes and their interactions are responsible. The scientists are investigating differences in skin aging processes observed between Europeans and the Chinese, i.e. their responses to environmental factors, and whether the relationships between environmental factors and ageing are affected by functionally relevant genetic markers. The results of this work will make a significant contribution to improving our knowledge of environmental factors and genetic factors and shed light on this biological mechanism. The answers to the questions asked will then help in the diagnosis and treatment of skin diseases.