Cell Dynamics are Influenced by Fluid Flow

Mechanical Engineering and Bioengineering
Massachusetts Institute of Technology

Abstract-
Vascular endothelial cells have been subjected to mechanical forces such as fluid shear stress and stretching of the substrate to which they are attached. The objective of these experiments has been to determine the cellular response to each different type of force. This talk will review some of the notable fluid flow experiments and their outcomes, and attempt to interpret these results from the point of view of the internal structure of the cell.

Actin filaments within the cell form an interconnected meshwork whose typical dimension is about 100 nm. This structure is in a continual state of dissolution and rebuilding; this allows the cells to change shape and be motile. Recent experiments show that the rate of actin turnover depends on the state of the cell as well as the forces applied to it. Confluent endothelial cells with no external forces are relatively quiescent, with long actin turnover times and little cell motion. The turnover rate increases when the cells are subjected to fluid shear stress or when cell-cell contacts are compromised. By studying the kinetics of actin polymerization (McGrath et al., to be submitted), it is possible to determine what reactions are promoted by the application of mechanical forces.

We postulate that it is stresses on the membrane-cytoskeleton attachment complexes that produce the changes in actin kinetics that are observed. The kinetic changes in turn lead to different internal structural configurations and actin turnover rates. While the exact signaling pathways are still somewhat elusive, the observed effects are reproducible and consistent with the postulated mechanism.

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