An analysis toolbox to explore mesenchymal migration heterogeneity reveals adaptive switching between distinct modes

ELife
Hamdah Shafqat-AbbasiStaffan Strömblad

Abstract

Mesenchymal (lamellipodial) migration is heterogeneous, although whether this reflects progressive variability or discrete, 'switchable' migration modalities, remains unclear. We present an analytical toolbox, based on quantitative single-cell imaging data, to interrogate this heterogeneity. Integrating supervised behavioral classification with multivariate analyses of cell motion, membrane dynamics, cell-matrix adhesion status and F-actin organization, this toolbox here enables the detection and characterization of two quantitatively distinct mesenchymal migration modes, termed 'Continuous' and 'Discontinuous'. Quantitative mode comparisons reveal differences in cell motion, spatiotemporal coordination of membrane protrusion/retraction, and how cells within each mode reorganize with changed cell speed. These modes thus represent distinctive migratory strategies. Additional analyses illuminate the macromolecular- and cellular-scale effects of molecular targeting (fibronectin, talin, ROCK), including 'adaptive switching' between Continuous (favored at high adhesion/full contraction) and Discontinuous (low adhesion/inhibited contraction) modes. Overall, this analytical toolbox now facilitates the exploration of both spontaneous a...Continue Reading

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Citations

Sep 1, 2016·Annual Review of Cell and Developmental Biology·Veronika Te BoekhorstPeter Friedl
Feb 9, 2017·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Prabhpreet K DhillonBingyun Sun
May 13, 2020·GigaScience·Alejandra N Gonzalez-BeltranLennart Martens
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Aug 2, 2018·Frontiers in Cellular Neuroscience·Alexa KissFriedrich Propst
Jul 3, 2019·Journal of Clinical Medicine·Sagar S Varankar, Sharmila A Bapat
Jan 30, 2021·Patterns·Aleix Boquet-PujadasNancy Guillén
Apr 21, 2021·Nature Materials·Kolade AdebowaleOvijit Chaudhuri
May 27, 2021·Current Protocols·Ellen T A DobsonKevin W Eliceiri
May 19, 2021·Cellular Signalling·Yasaswi Gayatri Mishra, Bramanandam Manavathi

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Methods Mentioned

BETA
GTPases
confocal microscopy
PCA

Software Mentioned

NIS
R
R Foundation for Statistical Computing
Cell Adhesion and Migration Analysis Toolbox
Elements
Matlab
Knime
PAD
RStudio
Matlab Toolbox

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