Computational model for autophagic vesicle dynamics in single cells

Katie R. Martin, Dipak Barua, Audra L. Kauffman, Laura M. Westrate, Richard G Posner, William S. Hlavacek, Jeffrey P. MacKeigan

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Macroautophagy (autophagy) is a cellular recycling program essential for homeostasis and survival during cytotoxic stress. This process, which has an emerging role in disease etiology and treatment, is executed in four stages through the coordinated action of more than 30 proteins. An effective strategy for studying complicated cellular processes, such as autophagy, involves the construction and analysis of mathematical or computational models. When developed and refined from experimental knowledge, these models can be used to interrogate signaling pathways, formulate novel hypotheses about systems, and make predictions about cell signaling changes induced by specific interventions. Here, we present the development of a computational model describing autophagic vesicle dynamics in a mammalian system. We used time-resolved, live-cell microscopy to measure the synthesis and turnover of autophagic vesicles in single cells. The stochastically simulated model was consistent with data acquired during conditions of both basal and chemicallyinduced autophagy. The model was tested by genetic modulation of autophagic machinery and found to accurately predict vesicle dynamics observed experimentally. Furthermore, the model generated an unforeseen prediction about vesicle size that is consistent with both published findings and our experimental observations. Taken together, this model is accurate and useful and can serve as the foundation for future efforts aimed at quantitative characterization of autophagy.

Original languageEnglish (US)
Pages (from-to)74-92
Number of pages19
JournalAutophagy
Volume9
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

Autophagy
Recycling
Microscopy
Homeostasis
Theoretical Models
Proteins

Keywords

  • Autophagy
  • Computational
  • Gillespie's method
  • LC3
  • Live-cell imaging
  • Mathematical
  • Microscopy
  • Quantitative biology
  • Single cell
  • Systems biology

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Martin, K. R., Barua, D., Kauffman, A. L., Westrate, L. M., Posner, R. G., Hlavacek, W. S., & MacKeigan, J. P. (2013). Computational model for autophagic vesicle dynamics in single cells. Autophagy, 9(1), 74-92. https://doi.org/10.4161/auto.22532

Computational model for autophagic vesicle dynamics in single cells. / Martin, Katie R.; Barua, Dipak; Kauffman, Audra L.; Westrate, Laura M.; Posner, Richard G; Hlavacek, William S.; MacKeigan, Jeffrey P.

In: Autophagy, Vol. 9, No. 1, 01.2013, p. 74-92.

Research output: Contribution to journalArticle

Martin, KR, Barua, D, Kauffman, AL, Westrate, LM, Posner, RG, Hlavacek, WS & MacKeigan, JP 2013, 'Computational model for autophagic vesicle dynamics in single cells', Autophagy, vol. 9, no. 1, pp. 74-92. https://doi.org/10.4161/auto.22532
Martin KR, Barua D, Kauffman AL, Westrate LM, Posner RG, Hlavacek WS et al. Computational model for autophagic vesicle dynamics in single cells. Autophagy. 2013 Jan;9(1):74-92. https://doi.org/10.4161/auto.22532
Martin, Katie R. ; Barua, Dipak ; Kauffman, Audra L. ; Westrate, Laura M. ; Posner, Richard G ; Hlavacek, William S. ; MacKeigan, Jeffrey P. / Computational model for autophagic vesicle dynamics in single cells. In: Autophagy. 2013 ; Vol. 9, No. 1. pp. 74-92.
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