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Metabolic imaging in multiple time scales

Authors
  • Ramanujan, V. Krishnan1, 2, 3, 2, 4, 2, 5, 2
  • 1 Metabolic Photonics Laboratory
  • 2 Cedars-Sinai Medical Center
  • 3 Department of Surgery
  • 4 Department of Biomedical Sciences
  • 5 Biomedical Imaging Research Institute
Type
Published Article
Journal
Methods
Publication Date
Jan 01, 2013
Volume
66
Issue
2
Pages
222–229
Identifiers
DOI: 10.1016/j.ymeth.2013.08.027
Source
Elsevier
Keywords
License
Unknown

Abstract

We report here a novel combination of time-resolved imaging methods for probing mitochondrial metabolism in multiple time scales at the level of single cells. By exploiting a mitochondrial membrane potential reporter fluorescence we demonstrate the single cell metabolic dynamics in time scales ranging from microseconds to seconds to minutes in response to glucose metabolism and mitochondrial perturbations in real time. Our results show that in comparison with normal human mammary epithelial cells, the breast cancer cells display significant alterations in metabolic responses at all measured time scales by single cell kinetics, fluorescence recovery after photobleaching and by scaling analysis of time-series data obtained from mitochondrial fluorescence fluctuations. Furthermore scaling analysis of time-series data in living cells with distinct mitochondrial dysfunction also revealed significant metabolic differences thereby suggesting the broader applicability (e.g. in mitochondrial myopathies and other metabolic disorders) of the proposed strategies beyond the scope of cancer metabolism. We discuss the scope of these findings in the context of developing portable, real-time metabolic measurement systems that can find applications in preclinical and clinical diagnostics.

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