[4]

Computational Modeling of Cell Responses to Mechanical Forces.

P.J. Prendergast¹ and J. Klein-Nulend^{2   1} Trinity Center for Bioengineering, School of Engineering, Trinity College, Dublin, Ireland; ²Department of Oral Cell Biology, ACTA-Vrije Universitiet Amsterdam, The Netherlands

   The objectives of this research are to better understand the role of mechanical forces in regulating expression of osteoblast-like cells. The methods used in the investigation coupled computer modeling of the cell using finite element analysis (FEA) with experimental approaches that stimulated confluent layers of cells under fluid flow or substrate cyclic strain (McGarry et al., FASEB Journal, 2005). The finite element model represented the structural features of the cell, including the cell membrane, cytoskeleton of actin filaments and microtubules (the latter formed into a tensegrity network ), and the cytoplasm and nucleus. A spread conformation was generated for the cell, and forces was applied of either (i) shear force on the surface to model stimulation by fluid flow or (ii) deformation at the substrate/cell boundary to model stimulation by substrate stretch.

   The experiments showed that fluid flow generating 0.6 MPa shear stress had a 7.1-fold and 3.3- fold increase in NO and PGE₂ production respectively whereas the response to 0.1% substrate strain was only 1.65-fold and 1.4-fold increase. On the other hand, the substrate strain had more than double the amount of Collagen Type 1 production relative to fluid flow. Differences in the outcome of mechanical stimulation by fluid flow versus substrate strain may be explained by FEA. The model shows an approximately 7.5-fold higher membrane stress due to fluid flow compared to substrate strain; therefore membrane stressing may be correlated with the release of these signaling molecules. The FEA model shows higher stresses on the cell substrate attachments under substrate strain compared to fluid flow indicating this is trans-membrane integrin may be involved in regulating collagen I production to mechanical strain.

Supported by the Programme for Research in Third Level Institutions in Ireland and the BITES project funded by the European Commission.