Zooming In On Mechanobiology

Look through a biology textbook and what do you see? Lots of molecules. Whether they involve drugs or DNA, discussions of biology often revolve around various versions of chemical reactions. However, when zooming way out, it is intuitive that biology is mechanical. After all, we can break bones, build muscle, and grow from babies into adults. This means that in certain ways, these chemical processes can be viewed as mechanical processes and visa versa.

The growing field of mechanobiology seeks to understand the ways in which biological systems use and are affected by mechanical means. Examples of biology using mechanics exist on many different scales, from dividing cells pushing against one another to exercise and mechanical loading speeding up the healing of orthopedic injuries. Certain processes in biology that are otherwise well-studied, such as neurons changing how they are connected so that you can learn, have mechanical aspects that are relatively neglected, in this case how those neurons move around to change their connections. One key finding in the field is that cells respond to the mechanical properties of their surroundings, such as how soft or stiff a surface is. Researchers have found that this stiffness can affect cell size, how fast cells grow, and even control the cells into which stem cells differentiate.

While many such effects have been observed, the exact mapping of these mechanical properties to the molecular-level changes across the whole cell has not been attempted. Publishing in the journal Biomaterials, researchers at Harvard University grew a particular type of stem cell in custom materials of different stiffnesses and used a technique called RNA-sequencing to get a broad snapshot of all of the processes in the cell that changed when the cells were in different environments.

These snapshots revealed that the activity of hundreds of genes was changed in these different environments and that certain of these genes only changed when the stiffness of the environment was in certain ranges. In other words, it is possible that depending on where this cell is in the body, the particular mechanical environment could help to control the cell’s function.

The researchers next looked for changes in the cells that they did not expect. Interestingly, they found that the stiffness changed the activity of genes involved in how these cells respond to inflammation. They then did a separate experiment where they cultured the cells in environments of different stiffnesses and added chemicals to simulate inflammation. In fact, the cells exposed to different stiffnesses responded very differently to the inflammatory signals.

While mechanobiology is still a young field, these results suggest that perhaps the mechanical aspects of biology act as a powerful layer of control and can even change how cells respond to drugs and other chemicals.

These findings are described in the article entitled RNA-seq reveals diverse effects of substrate stiffness on mesenchymal stem cells, recently published in the journal Biomaterials. This work was conducted by Max Darnell, Luo Gu, and David Mooney from Harvard University.