Multiscale Modeling of Primary Cilia - Multiscale Modeling in Biomechanics and Mechanobiology - page 82

Chapter 5
Multiscale Modeling of Primary Cilia

Y.-N. Young, Lina C. Espinha, An M. Nguyen and Christopher R. Jacobs

Abstract 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 a multifunctional antenna, sensing both mechan-
ical (fluid flow, pressure, touch, vibration) and chemical changes in the extracellular
environment. Furthermore, the primary cilium has also been implicated as a com-
plex signaling center for the cell, regulating key signaling pathways during devel-
opment such as Hedgehog and Wnt. In this article we summarize recent theoretical
approaches for modeling primary cilium bending mechanics. By combining theoret-
ical 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 incor-
porating the detailed basal anchorage in multiscale modeling 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.