Arterial endothelial cells (ECs) are subjected to pulsatile strain due to pressure
changes in the cardiac cycle and this may play a significant role in vascular function in
health and disease. Further, ECs differentially respond to different patterns of strain.
There is much evidence that cyclic uniaxial strain results in a perpendicular orientation of
ECs and their stress fibers, while no such alignment occurs in response to cyclic
equaibiaxial stretch. It is unclear how cells and their stress fibers determine their specific
response to particular spatiotemporal changes in the matrix, however. Given that ECs
located at regions in the arterial tree prone to atherogenesis are non-aglined, while ECs in
relatively healthy regions are oriented perpendicular to the principal direction of cyclic
stretch, it is important to understand the mechanisms which regulate stretch-induced
stress fiber alignment.
The focus of this thesis was to develop realistic models to describe the dynamic
changes in the organization of stress fibers in response to diverse spatiotemporal patterns
of stretch. The model is based on the premise that stress fibers are pre-stressed at a
?homeostatic? level so that stress fibers are extended beyond their unloaded lengths, and
that perturbation in stress fiber length from the homeostatic level destabilizes the stress fibers. A deterministic model described experimentally measured time courses of stress
fiber reorientation perpendicular to the direction of cyclic uniaxial stretch, as well as the
lack of alignment in response to equibiaxial stretch. In the case of cyclic simple
elongation with transverse matrix contraction, stress fibers oriented in the direction of
least perturbation in stretch. Model analysis indicated the need for a time-dependent
stress fiber mechanical property, however. Thus, a stochastic model was developed that
incorporated the concept that stress fibers tend to self-adjust to an equilibrium level of
extension when they are perturbed from their unload lengths with the turnover of stress
fibers. The stochastic model successfully described experimentally measured time
courses of stress fiber reorganization over a range of frequencies. At a frequency of 1 Hz,
stress fibers predominantly oriented perpendicular to stretch, while at 0.1 Hz the extent of
stress fiber alignment was markedly reduced and at 0.01 Hz there was no alignment at all.
Both the deterministic and stochastic models accurately described the relationship
between stretch magnitude and the extent of stress fiber alignment in endothelial cells
subjected to cyclic uniaxial stretch. Parameter sensitivity analyses for each model were
used to demonstrate the effects of each parameter on the characteristics of the system
response. In summary, the mathematical models were capable of describing stress fiber
reorganization in response to diverse temporal and spatial patterns of stretch. These
models provide a theoretical framework to elucidate the mechanisms by which adherent
cells sense the characteristics of matrix deformation and describe a mechanism by which
the cells can then adapt to such deformations to maintain mechanical homeostasis.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2009-08-7170 |
| Date | 14 January 2010 |
| Creators | Hsu, Hui-Ju |
| Contributors | Kaunas, Roland R. |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | Book, Thesis, Electronic Thesis |
| Format | application/pdf |
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