Cells respond to fluid shear stress but in a cell-type specific fashion. Endothelial cells elongate in the direction of shear, smooth muscle cells elongate also but perpendicular to shear. Cardiac myocytes do not change shape but shear modifies the beating rate of their sarcomeres. Activated leukocytes respond by retraction of pseudopods.

Several mechanisms have been proposed for the sensory mechanism to the weak forces associated with fluid shear stress (1 - 10 dyn/cm²) (e.g. glycocalyx bending and conformational changes in intracellular proteins, ion channel activity, shift in membrane fluidity, disruption of microtubules, deformations within the nucleus, constrained autocrine signaling).

We showed that G-protein coupled membrane receptor (GPCR) can serve as fluid shear sensors. Among the GPCRs in neutrophils, the formyl peptide receptor exhibits relatively high constitutive activity. Undifferentiated HL60 cells (a leukocyte tumor cell line that can be transfected) with lack of formyl peptide receptor form few pseudopods and no detectable response to fluid shear. Expression of formyl peptide receptor in undifferentiated HL60 cells caused pseudopod projection and robust pseudopod retraction during fluid shear. Knockdown of formyl peptide receptor with siRNA-transfected in differentiated HL60 cells exhibited no response to fluid shear. These results show that the formyl peptide receptor serves as a mechanosensor for fluid shear in neutrophils by decreasing its constitutive activity and reducing pseudopod projection.

Fluid shear stress may thus generate cell specific responses via the same signaling pathways that are used in nature by chemical ligands. This hypothesis has far reaching implications for biology and medicine.