Abstract
Computational modeling is an effective approach for simulating and predicting the development and remodeling of biological systems. Here, we propose to integrate a probabilistic mathematical modeling approach into an emerging bioengineering area known as molecular regenerative engineering. This experimental-computational framework can be used to simulate and predict the efficacy of molecular engineering in controlling and enhancing the regenerative processes of pathologically disordered cells, tissues and organs. We demonstrate the significance and principles of this approach by using a special case as an example: enhancement of endothelial cell adhesion to arterial constructs by siRNA-mediated modulation of an adhesion-inhibiting factor known as Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1. A continuum approach is used to model endothelial cell adhesion at the cellular level, while the Kramers reaction-rate theory is used to model cell adhesion at the subcellular and molecular levels. We show that the proposed computational model can potentially be used to simulate the processes and alterations of endothelial cell adhesion at the molecular and cellular levels under shear flow and to predict the effectiveness of siRNA-mediated SHP-1 knockdown in enhancing endothelial cell adhesion in arterial constructs. These preliminary investigations suggest that this integrated experimental-computational approach may be used for the simulation and prediction of regenerative processes in response to molecular engineering.
Original language | English (US) |
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Pages (from-to) | 2340-2352 |
Number of pages | 13 |
Journal | Computer Methods in Applied Mechanics and Engineering |
Volume | 197 |
Issue number | 25-28 |
DOIs | |
State | Published - Apr 15 2008 |
Funding
The support of this research by the National Science Foundation (NSF) is gratefully acknowledged.
Keywords
- Arterial reconstruction
- Atherosclerosis
- Endothelial cell adhesion
- Fluid-structure interaction
- Immersed finite element method
- Mesh-free method
- Reproducing kernel particle method
ASJC Scopus subject areas
- Computational Mechanics
- Mechanics of Materials
- Mechanical Engineering
- General Physics and Astronomy
- Computer Science Applications