Modeling Nuclear Damage from Cell Movement
Damaged hydrogels (DNA) with rotini (lamin proteins).Copyright 2020 Beth Hale, University of Pennsylvania RET
This engineering design activity simulates building a model to visualize and measure DNA damage within the nucleus as the cell migrates through the extracellular matrix (ECM). As students learn more about the structural composition of the ECM and the nucleus, they come to understand that both the ECM and the nucleus vary in stiffness and elasticity. Mechanobiologists have recently discovered that this feature plays an influential role in regulating numerous cell functions, as cells have the ability to “sense” their mechanical environment. The stiffness of the ECM is particularly important in the spread of cancer throughout the body. In this activity, students model the movement of a cell through a stiff matrix and measure the impact on the nucleus as DNA damage caused by the stress of this movement in relation to the amount of nuclear lamins, the major architectural proteins of the animal cell nucleus, present.
Mechanobiology is an emerging field of science that mixes biology, engineering, and physics. Mechanobiologists study how cells, tissues, and organs are constantly exposed to internal and external forces (or biomechanical cues) which guide and impact structure and function of those cells. Understanding what these biomechanical cues are and how cells respond has important implications for diseases such as cancer. Studying these forces provides insight on how cancers progress as well as on potential new treatments and therapies.
After this activity, students should be able to:
- Explain how there are tissues of varying stiffness in the human body.
- Describe how cells can become strained as they migrate through the extracellular matrix.
- Build a model that demonstrates how cell migration can lead to DNA damage due to the structural make-up of the nucleus and the surrounding forces acting upon the cell.
- Explain the connection between cell stress, DNA damage, and metastasis.
