Multiscale Modeling of Primary Cilia

Primary cilia are nonmotile, solitary organelles that protrude from the apical surface of nearly every mammalian cell. Discovered over a century ago, the primary cilium has been identified as amultifunctional antenna, sensing bothmechanical (fluid flow, pressure, touch, vibration) and chemical changes in the extracellular environment. Furthermore, the primary cilium has also been implicated as a complex signaling center for the cell, regulating key signaling pathways during development such as Hedgehog and Wnt. In this article we summarize recent theoretical approaches for modeling primary cilium bending mechanics. By combining theoretical modeling and detailed experimental observations, we construct a model for the primary cilium as an elastic slender beam with a nonlinear rotational stiffness at the base that accounts for the behavior of the basal anchorage. The importance of incorporating the detailed basal anchorage in multiscalemodeling of the primary cilium is highlighted by good quantitative agreement between cilium bending under flow and experimental observation. New observations further illustrate how the microtubule network connected to the basal body responds to mechanical stress from the bending of the primary cilium. We discuss how to use the current model as a foundation to construct a more realistic multiscale model that incorporates coupling with the cytoplasmic microtubule network.