Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.

We present an application of nonlinear image registration to align in microscopy time lapse sequences for every frame the cell outline and interior with the outline and interior of the same cell in a reference frame. The registration relies on a subcellular fiducial marker, a cell motion mask, and a...

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Main Authors: Xuexia Jiang, Tadamoto Isogai, Joseph Chi, Gaudenz Danuser
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-12-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1009667
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author Xuexia Jiang
Tadamoto Isogai
Joseph Chi
Gaudenz Danuser
author_facet Xuexia Jiang
Tadamoto Isogai
Joseph Chi
Gaudenz Danuser
author_sort Xuexia Jiang
collection DOAJ
description We present an application of nonlinear image registration to align in microscopy time lapse sequences for every frame the cell outline and interior with the outline and interior of the same cell in a reference frame. The registration relies on a subcellular fiducial marker, a cell motion mask, and a topological regularization that enforces diffeomorphism on the registration without significant loss of granularity. This allows spatiotemporal analysis of extremely noisy and diffuse molecular processes across the entire cell. We validate the registration method for different fiducial markers by measuring the intensity differences between predicted and original time lapse sequences of Actin cytoskeleton images and by uncovering zones of spatially organized GEF- and GTPase signaling dynamics visualized by FRET-based activity biosensors in MDA-MB-231 cells. We then demonstrate applications of the registration method in conjunction with stochastic time-series analysis. We describe distinct zones of locally coherent dynamics of the cytoplasmic protein Profilin in U2OS cells. Further analysis of the Profilin dynamics revealed strong relationships with Actin cytoskeleton reorganization during cell symmetry-breaking and polarization. This study thus provides a framework for extracting information to explore functional interactions between cell morphodynamics, protein distributions, and signaling in cells undergoing continuous shape changes. Matlab code implementing the proposed registration method is available at https://github.com/DanuserLab/Mask-Regularized-Diffeomorphic-Cell-Registration.
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spelling doaj.art-a578a16d6b3b4f64be128b8842cb3e762023-03-12T05:31:35ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582022-12-011812e100966710.1371/journal.pcbi.1009667Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.Xuexia JiangTadamoto IsogaiJoseph ChiGaudenz DanuserWe present an application of nonlinear image registration to align in microscopy time lapse sequences for every frame the cell outline and interior with the outline and interior of the same cell in a reference frame. The registration relies on a subcellular fiducial marker, a cell motion mask, and a topological regularization that enforces diffeomorphism on the registration without significant loss of granularity. This allows spatiotemporal analysis of extremely noisy and diffuse molecular processes across the entire cell. We validate the registration method for different fiducial markers by measuring the intensity differences between predicted and original time lapse sequences of Actin cytoskeleton images and by uncovering zones of spatially organized GEF- and GTPase signaling dynamics visualized by FRET-based activity biosensors in MDA-MB-231 cells. We then demonstrate applications of the registration method in conjunction with stochastic time-series analysis. We describe distinct zones of locally coherent dynamics of the cytoplasmic protein Profilin in U2OS cells. Further analysis of the Profilin dynamics revealed strong relationships with Actin cytoskeleton reorganization during cell symmetry-breaking and polarization. This study thus provides a framework for extracting information to explore functional interactions between cell morphodynamics, protein distributions, and signaling in cells undergoing continuous shape changes. Matlab code implementing the proposed registration method is available at https://github.com/DanuserLab/Mask-Regularized-Diffeomorphic-Cell-Registration.https://doi.org/10.1371/journal.pcbi.1009667
spellingShingle Xuexia Jiang
Tadamoto Isogai
Joseph Chi
Gaudenz Danuser
Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.
PLoS Computational Biology
title Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.
title_full Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.
title_fullStr Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.
title_full_unstemmed Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.
title_short Fine-grained, nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes.
title_sort fine grained nonlinear registration of live cell movies reveals spatiotemporal organization of diffuse molecular processes
url https://doi.org/10.1371/journal.pcbi.1009667
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