An experimental and computational analysis of primary cilia deflection under fluid flow

Downs, Matthew; Nguyẽ̂n, An; Herzog, Florian; Hoey, David A.; Jacobs, Christopher R.

doi:10.1080/10255842.2011.653784

Cited by 40 publications

(42 citation statements)

References 37 publications

(33 reference statements)

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“…Both bending and pivoting could trigger membrane channels. Previous studies have used fluid flow to estimate primary cilium bending stiffness based on deformation profiles (11)(12)(13)(14), but the precise mechanical properties of the cilium remain unknown. It is likely that mechanosensation needs subtle coordination and calibration of the intracellular machinery involving adaptation and feedback mechanisms reacting to external stimuli, such as is the case in mammalian inner-ear cells, where active mechanical processes are crucial for hearing acuity (15,16).…”

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confidence: 99%

Intracellular and extracellular forces drive primary cilia movement

Battle

Ott

Burnette

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Primary cilia are ubiquitous, microtubule-based organelles that play diverse roles in sensory transduction in many eukaryotic cells. They interrogate the cellular environment through chemosensing, osmosensing, and mechanosensing using receptors and ion channels in the ciliary membrane. Little is known about the mechanical and structural properties of the cilium and how these properties contribute to ciliary perception. We probed the mechanical responses of primary cilia from kidney epithelial cells [Madin-Darby canine kidney-II (MDCK-II)], which sense fluid flow in renal ducts. We found that, on manipulation with an optical trap, cilia deflect by bending along their length and pivoting around an effective hinge located below the basal body. The calculated bending rigidity indicates weak microtubule doublet coupling. Primary cilia of MDCK cells lack interdoublet dynein motors. Nevertheless, we found that the organelles display active motility. 3D tracking showed correlated fluctuations of the cilium and basal body. These angular movements seemed random but were dependent on ATP and cytoplasmic myosin-II in the cell cortex. We conclude that force generation by the actin cytoskeleton surrounding the basal body results in active ciliary movement. We speculate that actin-driven ciliary movement might tune and calibrate ciliary sensory functions.

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confidence: 99%

Intracellular and extracellular forces drive primary cilia movement

Battle

Ott

Burnette

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Careful measurements by several groups (6,16,17,27,55) have measured the flexural rigidity EI for primary cilia and while there is incomplete agreement, reported values typically vary within the range 1 Â 10 À23 < EI < 2 Â 10 À23 Nm 2 . Thus, we set EI ¼ 1.5 Â 10 À23 Nm 2 here.…”

Section: Classical Cantilever Beammentioning

confidence: 96%

Mechanical Properties of a Primary Cilium As Measured by Resonant Oscillation

Resnick

2015

Biophysical Journal

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Primary cilia are ubiquitous mammalian cellular substructures implicated in an ever-increasing number of regulatory pathways. The well-established ciliary hypothesis states that physical bending of the cilium (for example, due to fluid flow) initiates signaling cascades, yet the mechanical properties of the cilium remain incompletely measured, resulting in confusion regarding the biological significance of flow-induced ciliary mechanotransduction. In this work we measure the mechanical properties of a primary cilium by using an optical trap to induce resonant oscillation of the structure. Our data indicate 1) the primary cilium is not a simple cantilevered beam; 2) the base of the cilium may be modeled as a nonlinear rotatory spring, with the linear spring constant k of the cilium base calculated to be (4.6 ± 0.62) × 10(-12) N/rad and nonlinear spring constant α to be (-1 ± 0.34) × 10(-10) N/rad(2); and 3) the ciliary base may be an essential regulator of mechanotransduction signaling. Our method is also particularly suited to measure mechanical properties of nodal cilia, stereocilia, and motile cilia-anatomically similar structures with very different physiological functions.

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“…The first computational models of cilia bending in response to fluid flow estimate a bending stiffness on the order of 10 -23 N×m 2 , two orders of magnitude lower than motile cilia, and demonstrate that longer cilia experience greater deflection and thus membrane strain [7,67]. A more recent computational model incorporates fluid drag and allows for rotation at the base of the cilium, claiming a flexural rigidity an order of magnitude greater (10 -22 N×m 2 ) than previous models [68]. This difference is likely due to the use of different cell lines and different fluid flow conditions between each study, and also suggests that the cilium may not have a rigid attachment to the cell body and experiences some degree of basal rotation in response to fluid flow.…”

Section: Primary Cilia Structure Dictates Mechanosensingmentioning

confidence: 99%

“…Early electron micrographs of cilia structure actually suggest that cilia structure may not be constant along their length, and that cilia may lose microtubule symmetry and number towards the distal tip [71,72]. In fact, two of the described bending models also comment that cilia do not always appear to deflect with a constant curvature, potentially due to this lack of symmetry along the length of the cilium [67,68]. …”

Section: Primary Cilia Structure Dictates Mechanosensingmentioning

confidence: 99%

Primary cilia: Cell and molecular mechanosensors directing whole tissue function

Spasic

Jacobs

2017

Seminars in Cell & Developmental Biology

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Primary cilia are immotile, microtubule-based organelles extending from the surface of nearly every mammalian cell. Mechanical stimulation causes deflection of the primary cilium, initiating downstream signaling cascades to the rest of the cell. The cilium forms a unique subcellular microdomain, and defects in ciliary protein composition or physical structure have been associated with a myriad of human pathologies. In this review, we discuss the importance of ciliary mechanotransduction at the cell and tissue level, and how furthering our molecular understanding of primary cilia mechanobiology may lead to therapeutic strategies to treat human diseases.

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An experimental and computational analysis of primary cilia deflection under fluid flow

Cited by 40 publications

References 37 publications

Intracellular and extracellular forces drive primary cilia movement

Intracellular and extracellular forces drive primary cilia movement

Mechanical Properties of a Primary Cilium As Measured by Resonant Oscillation

Primary cilia: Cell and molecular mechanosensors directing whole tissue function

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