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

Author

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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)

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.

Suggested Citation

  • Chuangqi Wang & Hee June Choi & Sung-Jin Kim & Aesha Desai & Namgyu Lee & Dohoon Kim & Yongho Bae & Kwonmoo Lee, 2018. "Deconvolution of subcellular protrusion heterogeneity and the underlying actin regulator dynamics from live cell imaging," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04030-0
    DOI: 10.1038/s41467-018-04030-0
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