TY - JOUR
T1 - Profiling cellular morphodynamics by spatiotemporal spectrum decomposition
AU - Ma, Xiao
AU - Dagliyan, Onur
AU - Hahn, Klaus M.
AU - Danuser, Gaudenz
N1 - Funding Information:
The funding of this work is provided by NIH P01-GM103723 (to KMH and GD) and CISMM P41-EB002025 (to KMH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Hunter Elliott and Shann-Ching Chen for codes employed in the cell edge tracking and windowing modules.
Publisher Copyright:
© 2018 Ma et al. http://creativecommons.org/licenses/by/4.0/.
PY - 2018/8
Y1 - 2018/8
N2 - Cellular morphology and associated morphodynamics are widely used for qualitative and quantitative assessments of cell state. Here we implement a framework to profile cellular morphodynamics based on an adaptive decomposition of local cell boundary motion into instantaneous frequency spectra defined by the Hilbert-Huang transform (HHT). Our approach revealed that spontaneously migrating cells with approximately homogeneous molecular makeup show remarkably consistent instantaneous frequency distributions, though they have markedly heterogeneous mobility. Distinctions in cell edge motion between these cells are captured predominantly by differences in the magnitude of the frequencies. We found that acute photo-inhibition of Vav2 guanine exchange factor, an activator of the Rho family of signaling proteins coordinating cell motility, produces significant shifts in the frequency distribution, but does not affect frequency magnitude. We therefore concluded that the frequency spectrum encodes the wiring of the molecular circuitry that regulates cell boundary movements, whereas the magnitude captures the activation level of the circuitry. We also used HHT spectra as multi-scale spatiotemporal features in statistical region merging to identify subcellular regions of distinct motion behavior. In line with our conclusion that different HHT spectra relate to different signaling regimes, we found that subcellular regions with different morphodynamics indeed exhibit distinct Rac1 activities. This algorithm thus can serve as an accurate and sensitive classifier of cellular morphodynamics to pinpoint spatial and temporal boundaries between signaling regimes.
AB - Cellular morphology and associated morphodynamics are widely used for qualitative and quantitative assessments of cell state. Here we implement a framework to profile cellular morphodynamics based on an adaptive decomposition of local cell boundary motion into instantaneous frequency spectra defined by the Hilbert-Huang transform (HHT). Our approach revealed that spontaneously migrating cells with approximately homogeneous molecular makeup show remarkably consistent instantaneous frequency distributions, though they have markedly heterogeneous mobility. Distinctions in cell edge motion between these cells are captured predominantly by differences in the magnitude of the frequencies. We found that acute photo-inhibition of Vav2 guanine exchange factor, an activator of the Rho family of signaling proteins coordinating cell motility, produces significant shifts in the frequency distribution, but does not affect frequency magnitude. We therefore concluded that the frequency spectrum encodes the wiring of the molecular circuitry that regulates cell boundary movements, whereas the magnitude captures the activation level of the circuitry. We also used HHT spectra as multi-scale spatiotemporal features in statistical region merging to identify subcellular regions of distinct motion behavior. In line with our conclusion that different HHT spectra relate to different signaling regimes, we found that subcellular regions with different morphodynamics indeed exhibit distinct Rac1 activities. This algorithm thus can serve as an accurate and sensitive classifier of cellular morphodynamics to pinpoint spatial and temporal boundaries between signaling regimes.
UR - http://www.scopus.com/inward/record.url?scp=85053085730&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053085730&partnerID=8YFLogxK
U2 - 10.1371/journal.pcbi.1006321
DO - 10.1371/journal.pcbi.1006321
M3 - Article
C2 - 30071020
AN - SCOPUS:85053085730
VL - 14
JO - PLoS Computational Biology
JF - PLoS Computational Biology
SN - 1553-734X
IS - 8
M1 - e1006321
ER -