Force-Response Considerations in Ciliary Mechanosensation

Abstract

Considerable experimental evidence indicates that the primary, nonmotile cilium is a mechanosensory organelle in several epithelial cell types. As the relationship between cellular responses and nature and magnitude of applied forces is not well understood, we have investigated the effects of exposure of monolayers of renal collecting duct chief cells to orbital shaking and quantified the forces incident on cilia. An exposure of 24 h of these cells to orbital shaking resulted in a decrease of amiloride-sensitive sodium current by approximately 60% and ciliary length by approximately 30%. The sensitivity of the sodium current to shaking was dependent on intact cilia. The drag force on cilia due to induced fluid flow during orbital shaking was estimated at maximally 5.2x10(-3) pN at 2 Hz, approximately 4 times that of thermal noise. The major structural feature of cilia contributing to their sensitivity appears to be ciliary length. As more than half of the total drag force is exerted on the ciliary cap, one function of the slender stalk may be to expose the cap to greater drag force. Regardless, the findings indicate that the cilium is a mechanosensory organelle with a sensitivity much lower than previously recognized.

Effect of in vitro stress‐deprivation and cyclic loading on the length of tendon cell cilia in situ

“…34 While these load induced alterations in gene expression in tendon cells cannot be directly attributed to a mechanosensory function of the primary cilium, the affects of loading have been associated with changes in cilia length. 9,18,21,31,32 Tensile loading of rat tail tendons has been shown to result in fluid flow, 25,26 and cellular deformations. 24 Both of these mechanisms have previously been associated with a decrease in cilia length.…”

“…24 Both of these mechanisms have previously been associated with a decrease in cilia length. Fluid flow has been shown to decrease cilia lengths in renal cells 18,21,31,32 and loss of primary cilia from the endothelial surface of human umbilical cord cells. 19 Conversely, cyclic cellular deformation via compression loading of chondrocyte-agarose constructs significantly decreased lengthened cilia in free-swelling constructs.…”

“…19 Likewise, compressive loading of chondrocytes in a 3D agarose culture model has been shown to significantly reverse increases in cilia length in chondrocytes exposed to unloaded, free-swelling conditions. 9 While the precise mechanism(s) which trigger these changes in cilia length are unknown, it has been suggested that fluid flow and cell deformation are associated with decreases in cilia length, 9,[19][20][21] while increases in cilia length have been associated with cytoskeletal disruption. 22 Studies from our lab have shown that stress-deprivation (SD) of tendon cells has been associated with a disruption of cytoskeletal organization, 23 while tensile loading of tendons has been associated with cell deformation 24 and extracellular fluid flow.…”

<b>Developmental changes in primary cilia in the mouse tooth germ and oral </b><b>cavity </b>

“…Recent studies indicated a possible need to regulate the length of primary cilia in response to extracellular environmental changes. For instance, kidney cells can adjust the length of cilia in reaction to fluid stimuli; a deficiency in the regulation of the length and shape causes some disorders, termed ciliary diseases (14,21). Moreover, the primary cilium functions as a chemoreceptor which perceives the extracellular environment via membrane-bound receptors and ion channels expressed on cilia (23).…”

The primary cilium as a gravitational force transducer and a regulator of transcriptional noise

“…Algebraically: 1N ϭ 1(kg ‫ء‬ m)/s 2 Thus, a typical cell could exert up to 1,047 ϫ 10 -15 N on its primary cilium due to the relative positions of the Earth, Sun, and Moon, depending on the orientation of the cell in the gravitational field with respect to its primary cilium. Interestingly, a single primary cilium is capable of detecting a shear force of 5.2 ϫ 10 -15 N (Resnick and Hopfer, 2007). This suggests that the primary cilium is sensitive enough to detect the cyclic change in Earth's gravitational field.…”