Sara Wickström, cell biologist: ‘Cells do not just follow chemical orders; they also sense the forces around them’

For decades, scientists viewed biology as a chemical process. Cells made decisions based on instructions written in their genes, executed through chemical signals. However, Finnish researcher Sara Wickström has revealed a crucial missing piece in this story: cells also sense the mechanical forces around them. Cells do not merely follow chemical and genetic instructions; they interpret the physical properties of their environment.

Wickström, director of the Max Planck Institute for Molecular Biomedicine in Münster, demonstrated that these physical signals can reach the cell nucleus, where DNA is stored, and alter gene behavior. For her groundbreaking work, she was awarded the prestigious Körber Prize, a €1 million ($1.16 million) honor that has previously been awarded to eight Nobel laureates.

The Finnish scientist drew a comparison between eyelid skin and skin on the soles of the feet. Both are made of the same cell types, yet one is thin and flexible, while the other is thick and tough. The cells know which structure to build due to the unique mechanical forces they experience. Wickström's most influential finding was that applying mechanical forces to skin stem cells triggered a large-scale reorganization of DNA packaging within the nucleus.

This discovery marks the beginning of a new field at the intersection of physics and biology known as mechanobiology. Every cell in the body has the same DNA but performs different functions because it decides which genes to express. Traditionally, gene regulation was thought to be purely biochemical. However, Wickström and her team have shown that mechanical forces also play a critical role, although these forces must first be converted into biochemical signals to regulate chromatin — DNA combined with proteins that organize it and regulate gene expression.

When Wickström discusses mechanical forces, she refers to the same forces we experience, albeit on a cellular scale. These forces, such as pressure, stretching, or stiffness, can influence cell structure and function, even in different parts of the body. For example, shear stress in blood vessels or muscle stretching impacts the functional specialization of cells.

The researchers found that the declining function of skin stem cells with age is not due to defective stem cells but rather changes in the mechanical properties of their microenvironment. This finding has significant medical implications. Instead of solely focusing on transplanting or rejuvenating the cells themselves, the surrounding connective tissue also needs to be addressed to maintain the cells' function.

Wickström's research is already translating into potential applications. Her team is working on two main fronts: cancer treatment and diagnostics. In cancer, altered mechanical properties of the tumor and its microenvironment may contribute to the aggressiveness of the disease. The researchers are also developing biomarkers based on these mechanical changes to predict tumor behavior. They have even founded a spin-off company to translate these biomarkers into clinical practice.

As for potential treatments, Wickström envisions two possibilities: developing small molecules that modify how mechanical forces reprogram cells or directly altering how cells respond to mechanical forces. The latter is still a distant possibility. The implications of these findings are vast, ranging from cancer treatment to diagnostics, and even the development of new therapeutic strategies.