Description
- Abstract:
- Forces play an important role in physiology and pathology. Throughout development, cellular forces aid in the creation of tissues and organs. In wound healing, cellular forces result in wound closure but these forces in excess are implicated in fibrosis. Due to the importance of forces, much research has focused on quantifying these forces. Despite the number of 2D and 3D assays to measure cellular forces, most of the approaches have focused on the forces generated by cells on an extracellular matrix (ECM). Using reductionist approaches, much research has focused on measuring the forces and energies associated with the binding of the proteins involved in cellular contraction. However, there is little research about the forces and energies of these proteins working in concert. Needed is a systems biology approach to measure forces and energies in 3D tissues where cell-cell interactions dominate. Using 3D self-assembled toroid shaped microtissues, we developed an assay to measure the power associated with cell-cell adhesion. The assay takes a systems biology approach to measure how much power is exerted by cells as they self-assemble into toroid shaped microtissues and ascend a conical hydrogel peg. This novel approach allows the user to examine cell-cell forces in a 3D environment in a completely non-invasive and straightforward manner. The assay requires no instrument calibration and does not contact or manipulate samples, which can alter cell behavior. Using the assay, we have quantified and compared the self-assembly of normal human fibroblasts, a rat hepatocyte cell line, and their mixes. As well, we have used the assay to tease out the role of active cellular contraction and how it contributes to the power generation of both these cell types. Using this assay we have determined the importance of contractile forces in the self-assembly of cells, the role of heterotypic cell interactions in inducing cell power and its synergistic effect with transforming growth factor-beta1. In addition to these findings, we foresee this assay as being useful for a number of applications including discovering anti-fibrotic therapies, studying cancer cell metastasis, and examining self-sorting.
- Notes:
- Thesis (Ph.D. -- Brown University (2012)
Access Conditions
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- In Copyright
- Restrictions on Use
- Collection is open for research.
Citation
Youssef, Jacquelyn,
"Quantifying Cellular Forces in 3D Self-Assembled Microtissues"
(2012).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0RX99DQ
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....