Deconvolution of subcellular protrusion heterogeneity and the underlying actin regulator dynamics from live cell imaging

Chuangqi Wang, Hee June Choi, Sung-Jin Kim, Aesha Desai, Namgyu Lee, Dohoon Kim, Yongho Bae and Kwonmoo Lee ()
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Chuangqi Wang: Worcester Polytechnic Institute
Hee June Choi: Worcester Polytechnic Institute
Sung-Jin Kim: Worcester Polytechnic Institute
Aesha Desai: University at Buffalo, State University of New York
Namgyu Lee: University of Massachusetts Medical School
Dohoon Kim: University of Massachusetts Medical School
Yongho Bae: University at Buffalo, State University of New York
Kwonmoo Lee: Worcester Polytechnic Institute

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: Abstract Cell protrusion is morphodynamically heterogeneous at the subcellular level. However, the mechanism of cell protrusion has been understood based on the ensemble average of actin regulator dynamics. Here, we establish a computational framework called HACKS (deconvolution of heterogeneous activity in coordination of cytoskeleton at the subcellular level) to deconvolve the subcellular heterogeneity of lamellipodial protrusion from live cell imaging. HACKS identifies distinct subcellular protrusion phenotypes based on machine-learning algorithms and reveals their underlying actin regulator dynamics at the leading edge. Using our method, we discover “accelerating protrusion”, which is driven by the temporally ordered coordination of Arp2/3 and VASP activities. We validate our finding by pharmacological perturbations and further identify the fine regulation of Arp2/3 and VASP recruitment associated with accelerating protrusion. Our study suggests HACKS can identify specific subcellular protrusion phenotypes susceptible to pharmacological perturbation and reveal how actin regulator dynamics are changed by the perturbation.

Date: 2018
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DOI: 10.1038/s41467-018-04030-0

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