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Hydrogel Elastic Energy: A Stressor Triggering an Adaptive Stress-Mediated Cell Response
Sara Lipari1, Pasquale Sacco1, Michela Cok1
1Department of Life Sciences, University of Trieste, Via L. Giorgieri 5, Trieste, 34127, Italy.
Advanced Healthcare Materials
|November 13, 2024
Summary
Cellular responses in 3D cultures are influenced by extracellular matrix (ECM) elastic energy. Higher elastic energy increases cellular stress, leading to stress granules and altered alkaline phosphatase (ALP) activity.
Area of Science:
- Biomaterials Science
- Cell Biology
- Mechanobiology
Background:
- Cell-extracellular matrix (ECM) interactions are bidirectional, involving cellular forces and microenvironmental resistance.
- ECM properties like stiffness, viscoelasticity, and deformation significantly impact cellular behavior.
- Existing research highlights the importance of mechanical cues in cell responses.
Purpose of the Study:
- To introduce and define 'elastic energy' as a combined measure of ECM mechanical properties.
- To investigate the role of elastic energy as a mechanical feedback influencing cell responses in 3D cultures.
- To elucidate the relationship between elastic energy, cellular stress, and specific molecular pathways.
Main Methods:
- Development of the concept of elastic energy integrating ECM stiffness, viscoelasticity, and deformation.
- Utilizing 3D cell culture models to assess cellular responses to varying matrix elastic energies.
- Analyzing cellular stress markers, including G3BP-mediated stress granules, alkaline phosphatase (ALP) activity, gene expression, and Yes-associated protein (YAP) nuclear translocation.
Main Results:
- Elastic energy acts as a significant stress factor for cells in 3D cultures.
- Increased matrix elastic energy correlates with elevated cellular stress and the formation of G3BP-mediated stress granules.
- Higher elastic energy is associated with increased ALP activity and decreased gene expression.
- Nuclear translocation of YAP mediates the observed cellular responses.
Conclusions:
- Elastic energy is a critical parameter that encapsulates the mechanical feedback cells receive from the ECM.
- This mechanical feedback, quantified as elastic energy, directly influences cellular stress states in 3D environments.
- The findings underscore the importance of considering elastic energy as a key regulator of cellular stress and behavior in biomaterial and tissue engineering applications.
