Abstract:
:Motile cilia are essential for clearance of particulates and pathogens from airways. For effective transport, ciliary motor proteins and axonemal structures interact to generate the rhythmic, propulsive bending, but the mechanisms that produce a dynamic waveform remain incompletely understood. Biomechanical measures of human ciliary motion and their relationships to ciliary assembly are needed to illuminate the biophysics of normal ciliary function and to quantify dysfunction in ciliopathies. To these ends, we analyzed ciliary motion by high-speed video microscopy of ciliated cells sampled from human lung airways compared with primary culture cells that undergo ciliogenesis in vitro. Quantitative assessment of waveform parameters showed variations in waveform shape between individual cilia; however, general trends in waveform parameters emerged, associated with progression of cilia length and stage of differentiation. When cilia emerged from cultured cells, beat frequency was initially elevated, then fell and remained stable as cilia lengthened. In contrast, the average bending amplitude and the ability to generate force gradually increased and eventually approached values observed in ex vivo samples. Dynein arm motor proteins DNAH5, DNAH9, DNAH11, and DNAH6 were localized within specific regions of the axoneme in the ex vivo cells; however, distinct stages of in vitro waveform development identified by biomechanical features were associated with the progressive movement of dyneins to the appropriate proximal or distal sections of the cilium. These observations suggest that the stepwise variation in waveform development during ciliogenesis is dependent on cilia length and potentially on outer dynein arm assembly.
journal_name
Am J Respir Cell Mol Biolauthors
Oltean A,Schaffer AJ,Bayly PV,Brody SLdoi
10.1165/rcmb.2017-0436OCsubject
Has Abstractpub_date
2018-10-01 00:00:00pages
511-522issue
4eissn
1044-1549issn
1535-4989journal_volume
59pub_type
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