Cyclic AMP-dependent cell shape changes induced by mechanical forces

Biomaterials used in some biomedical devices are exposed to flow of physiological fluids. The flow-induced forces may influence the morphological and the biochemical responses of adhering cells. The objective of this work is to examine the capacity of a mechanical stress to cause changes in cell/substratum and cell/cell interactions via the second messenger cAMP pathway (cyclic Adenosine Monophosphate). Cyclic AMP is known to modulate cell shape, cell adhesion and intercellular communication in static conditions. A specially designed flow chamber was used to analyze the responses of mouse 3T3 fibroblasts spread on biocompatible substrata and submitted to controlled shear stresses. A 1.1-Pa shear stress induced: cell rounding, disruption of vitronectin receptors clusters and clustering of connexins 43 at cell-cell apposition points. These cell responses were cAMP-dependent. These investigations should help provide a better understanding of the early biochemical events triggered by mechanical forces.