Biophysics and biofluid dynamics of primary cilia: evidence for and against the flow-sensing function

Primary cilia have been called "the forgotten organelle" for over 20 yr. As cilia now have their own journal and several books devoted to their study, perhaps it is time to reconsider the moniker "forgotten organelle." In fact, during the drafting of this review, 12 relevant publications have been issued; we therefore apologize in advance for any relevant work we inadvertently omitted. What purpose is yet another ciliary review? The primary goal of this review is to specifically examine the evidence for and against the hypothesized flow-sensing function of primary cilia expressed by differentiated epithelia within a kidney tubule, bringing together differing disciplines and their respective conceptual and experimental approaches. We will show that understanding the biophysics/biomechanics of primary cilia provides essential information for understanding any potential role of ciliary function in disease. We will summarize experimental and mathematical models used to characterize renal fluid flow and incident force on primary cilia and to characterize the mechanical response of cilia to an externally applied force and discuss possible ciliary-mediated cell signaling pathways triggered by flow. Throughout, we stress the importance of separating the effects of fluid shear and stretch from the action of hydrodynamic drag.