By: Annie Hu
You may have heard of the field of Biomechanics: the study of the structure, function, and motion of our biological systems. Biomechanics studies the physics and the movements of the body, and applies mechanical engineering principles to study the physiology of our cells, tissues, and organs. For example, take human movement, which is essentially the result of many interactions between our muscles, bones, ligaments, and joints. By analyzing and observing how forces play a role in how we move and their effects on our musculoskeletal system, we can observe common injuries and figure out new ways to modify or control the mechanical environment in order to allow for better treatments, rehabilitation, and prevention.
We’ve only just scratched the surface of what Biomechanics is and its potential uses. But an emerging and perhaps less known field of biomedical and bioengineering research is that of MechanoBiology. While Biomechanics involves much of manipulating and testing of the forces acting upon biological structures, mechanobiology focuses instead on observing how physical cues affect behavior.
What does this mean? It had been hypothesized for some time that mechanical forces and physical cues can actually drive the formation and/or responses of biological structures. However, only recently, as a result of newer and more developed technologies, researchers have begun to see how biological structures, especially cells, seem to transduce mechanical forces and stimuli into biochemical signals. When cells sense and transduce these mechanical forces, this is known as mechanotransduction at the cellular level. To get an idea of how mechanotransduction at the cellular level works, let’s take the example of an experiment conducted on mesenchymal stem cells, which are a type of multipotent adult stem cell that can differentiate into bone, cartilage, muscle, and fat cells. The experiment described (Engler et al 2006) tested how the microenvironment surrounding mesenchymal stem cells could affect what the cells specialise into.
What is the environment surrounding cells made up of? Tissues are made up not only of cells, but also of the space in between their cells, and this space includes what is known as the extracellular matrix. The extracellular matrix in connective tissue can determine what the tissue’s physical properties will be. Some of these physical properties include the tissue’s stiffness and elasticity. Physical properties will differ from tissue type to tissue type. For example, soft matrices are present in the brain, stiffer matrices are in our muscles, and very stiff and rigid matrices are present in bones.
A part of the experiment observed how matrix elasticity affected naive mesenchymal stem cell differentiation. This was achieved by culturing cells in different environments that mimicked the stiffness of a certain tissue type. Intriguingly, it was found that when these stem cells were cultured in environments representative of the stiffness/elasticity of different types of tissue, they began to display features of the cells present within the tissue that their new environment mimicked. Cells grown in a softer environment like that of the brain started to show characteristics similar to cells present in the brain, while those grown in a stiffer environment like that in muscle tissues showed characteristics of muscle cells, and the ones grown in a rigid environment began to take on the form of bone cells.
You can see how the cells seemed to transduce the mechanical stimuli of their environment into biochemical signals, indicating which type of cell to differentiate into. This is a great example of what MechanoBiology is, the science of how physical cues can affect the behavior of biological structures, just like how the environment affected the differentiation of the mesenchymal stem cells. Understanding mechanotransduction could be essential to creating new and improved therapeutic treatments for many of the diseases and health problems that plague us. We could potentially change stem cell fate by determining the type of cell they are to become; we could learn to use mechanical signals to our advantage in order to hinder disease progression, regulate cell behavior, and promote regeneration. There is so much yet to uncover in the exciting, growing field of MechanoBiology!
If you are curious about the mesenchymal stem cell experiment, you can read about it here! Thank you so much for reading, and I hope that I was able to help you learn more about this extremely fascinating science!
Definitions:
Physiology- How an organism or body part works
Transduce- To convert into another form
Mechanotransduction- The transduction of mechanical forces and stimuli
Multipotent- Cells that self renew or differentiate into the specialised cells types within a specific tissue.
Differentiate- The process in which a stem cell becomes a cell with a specific function, such as a brain cell, blood cell, etc.
Extracellular Matrix(ECM)- refers to the network of macromolecules that support surrounding cells structurally and biochemically.
Stiffness- How hard it is to make a certain material bend or break
Elasticity- the ability to return to the original state after some force is applied (stretched, compressed)
Naive- a naive stem cell can differentiate into almost any kind of cell. A type of pluripotent stem cell
What Did You Learn?
Questions:
1. What is the difference between Biomechanics and MechanoBiology?
Biomechanics focuses more heavily on how forces play a role in how we move and their effects on our biological systems and structures. It involves a lot of manipulating and testing of these forces. Mechanobiology focuses more heavily on the response of biological structures like cells to mechanical stimuli.
2. How did mechanotransduction at the cellular level affect the differentiation of the mesenchymal stem cells?
Mechanotransduction is the conversion of mechanical stimuli to biochemical signals. In this case, the mechanical stimulus was the stiffness/elasticity of the tissue matrix. The stem cells were able to sense this stimulus and converted it into a signal which directed the cell to a certain specification. For example, if the stiffness/elasticity of the environment around the stem cell seemed to mimic the matrix of muscle tissue, the cell began to take on some characteristics of a muscle cell.
Citations:
Sites:
Papers:
Engler A.J., Sen S., Sweeney H.L., Discher D.E. (2006). Matrix Elasticity Directs Stem Cell Lineage Specification. Cell, 126(4), 677-689. Matrix Elasticity Directs Stem Cell Lineage Specification
Lu TW, Chang CF. Biomechanics of human movement and its clinical applications. Kaohsiung J Med Sci. 2012;28(2 Suppl):S13-S25. doi:10.1016/j.kjms.2011.08.004
Eyckmans, J., Boudou, T., Yu, X., & Chen, C. S. (2011). A hitchhiker's guide to mechanobiology. Developmental cell, 21(1), 35–47. Perspective A Hitchhiker's Guide to Mechanobiology
Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science; 2002. The Extracellular Matrix of Animals. Available from: The Extracellular Matrix of Animals - Molecular Biology of the Cell
Images: by Annie Hu