title: Mechanical properties of primary cilia regulate the response to fluid flow.
abstract: The primary cilium is a ubiquitous organelle present on most mammalian cells. Malfunction of the organelle has been associated with various pathological disorders, many of which lead to cystic disorders in liver, pancreas, and kidney. Primary cilia have in kidney epithelial cells been observed to generate intracellular calcium in response to fluid flow, and disruption of proteins involved in this calcium signaling lead to autosomal dominant polycystic kidney disease, implying a direct connection between calcium signaling and cyst formation. It has also been shown that there is a significant lag between the onset of flow and initiation of the calcium signal. The present study focuses on the mechanics of cilium bending and the resulting calcium signal. Visualization of real-time cilium movements in response to different types of applied flow showed that the bending is fast compared with the initiation of calcium increase. Mathematical modeling of cilium and surrounding membrane was performed to deduce the relation between bending and membrane stress. The results showed a delay in stress buildup that was similar to the delay in calcium signal. Our results thus indicate that the delay in calcium response upon cilia bending is caused by mechanical properties of the cell membrane.
authors.affiliation: Division of Cell Physics, Department of Applied Physics, Royal Institute of Technology, Stockholm, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Rydholm
authors.forename: Gordon
authors.initials: G
authors.lastname: Zwartz
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Kowalewski
authors.forename: Padideh
authors.initials: P
authors.lastname: Kamali-Zare
authors.forename: Thomas
authors.initials: T
authors.lastname: Frisk
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Brismar
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002923:Cilia / Q000502:physiology*; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D057446:Hydrodynamics; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D023421:Models, Animal; D008962:Models, Theoretical; D015398:Signal Transduction / Q000502:physiology