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

Journal: Nature communications
PMID: 29703977

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.

Authors

  • Chuangqi Wang
    Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, 01609, USA.
  • Hee June Choi
    Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, 01609, USA.
  • Sung-Jin Kim
    Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, 01609, USA.
  • Aesha Desai
    Department of Pathology and Anatomical Sciences, Computational Cell Biology, Anatomy and Pathology Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14203, USA.
  • Namgyu Lee
    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
  • Dohoon Kim
    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01655, USA.
  • Yongho Bae
    Department of Pathology and Anatomical Sciences, Computational Cell Biology, Anatomy and Pathology Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14203, USA.
  • Kwonmoo Lee
    Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, 01609, USA. klee@wpi.edu.

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