Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells.

Nat Commun 2019 04 16;10(1):1763. Epub 2019 Apr 16.

Biological and Soft Systems Sector, Cavendish Laboratory, University of Cambridge, Cambridge, CB3 0HE, UK.

Personalized approaches for systematically assessing ciliary beat dynamics and for drug testing would improve the challenging task of diagnosing and treating respiratory disorders. In this pilot study, we show how multiscale differential dynamic microscopy (multi-DDM) can be used to characterize collective ciliary beating in a non-biased automated manner. We use multi-DDM to assess the efficacy of different CFTR-modulating drugs in human airway epithelial cells derived from subjects with cystic fibrosis (ΔF508/ΔF508 and ∆F508/-) based on ciliary beat frequency and coordination. Similar to clinical observations, drug efficacy is variable across donors, even within the same genotype. We show how our assay can quantitatively identify the most efficient drugs for restoring ciliary beating for each individual donor. Multi-DDM provides insight into ciliary beating responses following treatment with drugs, and has application in the broader context of respiratory disease and for drug screening.

Download full-text PDF

Source
http://www.nature.com/articles/s41467-019-09798-3
Publisher Site
http://dx.doi.org/10.1038/s41467-019-09798-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467870PMC
April 2019
7 Reads

Publication Analysis

Top Keywords

ciliary beating
12
cystic fibrosis
8
epithelial cells
8
ciliary beat
8
ciliary
5
subjects cystic
4
derived subjects
4
cells derived
4
fibrosis Δf508/Δf508
4
∆f508/- based
4
coordination clinical
4
clinical observations
4
frequency coordination
4
beat frequency
4
airway epithelial
4
based ciliary
4
Δf508/Δf508 ∆f508/-
4
drugs human
4
characterize collective
4
collective ciliary
4

References

(Supplied by CrossRef)
Article in N. Engl. J. Med.
RS Schwartz et al.
N. Engl. J. Med. 2011
Article in N. Engl. J. Med.
JV Fahy et al.
N. Engl. J. Med. 2010
Article in Sci. Transl. Med.
SP Quinn et al.
Sci. Transl. Med. 2015
Article in Eur. Arch. Otorhinolaryngol.
G Mantovani et al.
Eur. Arch. Otorhinolaryngol. 2010
Article in Am. J. Physiol. Lung Cell. Mol. Physiol.
PR Sears et al.
Am. J. Physiol. Lung Cell. Mol. Physiol. 2011
Article in Biophys. J.
L Feriani et al.
Biophys. J. 2017
Article in Nat. Rev. Genet.
GR Cutting et al.
Nat. Rev. Genet. 2014
Article in Eur. Biophys. J.
M Ryser et al.
Eur. Biophys. J. 2007
Article in Cells Tissues Organs
G Schätz et al.
Cells Tissues Organs 2013
Article in PLoS Comput. Biol.
PA Vasquez et al.
PLoS Comput. Biol. 2016

Similar Publications