MECHANISM FOR HETEROGENEOUS ENDOTHELIAL RESPONSES TO FLOW IN-VIVO ANDIN-VITRO

Exposure of endothelium to a nominally uniform flow field in vivo and in vitro frequently results in a heterogeneous distribution of individ ual cell responses. Extremes in response levels are often noted in nei ghboring cells. Such variations are important for the spatial interpre tation of vascular responses to flow and for an understanding of mecha notransduction mechanisms at the level of single cells. We propose tha t variations of local forces defined by the cell surface geometry cont ribute to these differences. Atomic force microscopy measurements of c ell surface topography in living endothelium both in vitro and in situ combined with computational fluid dynamics demonstrated large cell-to -cell variations in the distribution of flow-generated shear stresses at the endothelial luminal surface. The distribution of forces through out the surface of individual cells of the monolayer was also found to vary considerably and to be defined by the surface geometry. We concl ude that the endothelial three-dimensional surface geometry defines th e detailed distribution of shear stresses and gradients at the single cell level, and that there are large variations in force magnitude and distribution between neighboring cells. The measurements support a to pographic basis for differential endothelial responses to how observed in vivo and in vitro. Included in these studies are the first prelimi nary measurements of the living endothelial cell surface in an intact artery.