@article{837d438c08d4418d803a843fd59b42d3,
title = "Robust and automated detection of subcellular morphological motifs in 3D microscopy images",
abstract = "Rapid developments in live-cell three-dimensional (3D) microscopy enable imaging of cell morphology and signaling with unprecedented detail. However, tools to systematically measure and visualize the intricate relationships between intracellular signaling, cytoskeletal organization and downstream cell morphological outputs do not exist. Here, we introduce u-shape3D, a computer graphics and machine-learning pipeline to probe molecular mechanisms underlying 3D cell morphogenesis and to test the intriguing possibility that morphogenesis itself affects intracellular signaling. We demonstrate a generic morphological motif detector that automatically finds lamellipodia, filopodia, blebs and other motifs. Combining motif detection with molecular localization, we measure the differential association of PIP2 and KrasV12 with blebs. Both signals associate with bleb edges, as expected for membrane-localized proteins, but only PIP2 is enhanced on blebs. This indicates that subcellular signaling processes are differentially modulated by local morphological motifs. Overall, our computational workflow enables the objective, 3D analysis of the coupling of cell shape and signaling.",
author = "Driscoll, {Meghan K.} and Welf, {Erik S.} and Jamieson, {Andrew R.} and Dean, {Kevin M.} and Tadamoto Isogai and Reto Fiolka and Gaudenz Danuser",
note = "Funding Information: This research was funded by grants from the Cancer Prevention Research Institute of Texas (nos. RR160057 to R.F. and R1225 to G.D.) and the National Institutes of Health (nos. F32GM116370 and K99GM123221 to M.K.D., K25CA204526 to E.S.W., F32GM117793 to K.M.D., R33CA235254 to R.F. and R01GM067230 to G.D.). Confocal imaging was performed at the UT Southwestern Live Cell Imaging Facility. Most surface renderings were performed using UCSF ChimeraX, which was developed by the Resource for Biocomputing, Visualization and Informatics at the University of California, San Francisco (supported by grant no. P41GM103311). We thank T. Goddard for assistance with ChimeraX, as well as I. de Vries, J. Renkawitz and M. Sixt for assistance differentiating dendritic cells. We would also like to thank F. Peri (University of Zurich) and members of her laboratory, especially M. Albert, for the unpublished images of microglia cells. We also thank P. Friedl (MD Anderson Cancer Center) for the MV3 melanoma cells, S. Morrison (UT Southwestern) for the primary melanoma cells, M. Sixt (IST Austria) for the dendritic cell precursors, J. Minna and J. Shay (UT Southwestern) for the transformed HBEC cells and R. McIntosh (University of Colorado, Boulder) for the U2OS osteosarcoma cells. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = oct,
day = "1",
doi = "10.1038/s41592-019-0539-z",
language = "English (US)",
volume = "16",
pages = "1037--1044",
journal = "Nature methods",
issn = "1548-7091",
publisher = "Public Library of Science",
number = "10",
}