Force generation and dynamics of individual cilia under external loading.
Motile cilia are unique multimotor systems that display coordination and periodicity while imparting forces to biological fluids. They play important roles in normal physiology, and ciliopathies are implicated in a growing number of human diseases. In this work we measure the response of individual human airway cilia to calibrated forces transmitted via spot-labeled magnetic microbeads. Cilia respond to applied forces by 1), a reduction in beat amplitude (up to an 85% reduction by 160-170 pN of force); 2), a decreased tip velocity proportionate to applied force; and 3), no significant change in beat frequency. Tip velocity reduction occurred in each beat direction, independently of the direction of applied force, indicating that the cilium is "driven" in both directions at all times. By applying a quasistatic force model, we deduce that axoneme stiffness is dominated by the rigidity of the microtubules, and that cilia can exert 62 +/- 18 pN of force at the tip via the generation of 5.6 +/- 1.6 pN/dynein head.
Hill
David B
DB
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Swaminathan
Vinay
V
Estes
Ashley
A
Cribb
Jeremy
J
O'Brien
E Timothy
ET
Davis
C William
CW
Superfine
R
R
D002478:Cells, Cultured; D002923:Cilia / Q000502:physiology*; D003198:Computer Simulation; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D013314:Stress, Mechanical