MRC National Institute for Medical Research, London
Science for Health
Quantitative imaging of metabolism: seeing is believing
20 January 2012
Mass spectrometry is a powerful technique for measuring the abundance of molecules, but it has usually been limited to the analysis of bulk tissues or cells. Given that cells within a tissue are often different from one another, a long-standing aim has been to marry mass spectrometry with microscopy, in such a way that molecules can be quantified within individual cells with high spatial resolution.
Multi-isotope imaging mass spectrometry (MIMS), a technique developed by Claude Lechene from Harvard Medical School, combines ion microscopy, secondary ion mass spectrometry, stable isotope reporters and computational analysis. This allows biologists to image and measure stable isotope labels at numerous different points within a cell with a spatial resolution of ~30 nanometres. MIMS is therefore particularly valuable for analysing very small samples such as minute pieces of biopsied tissue or tiny animal embryos.
Andrew Bailey and Alex Gould (pictured), from NIMR's Division of Physiology and Metabolism, have collaborated with Claude Lechene and colleagues in proof-of-principle studies applying MIMS to the analysis of lipid metabolism. They used the fruit fly (Drosophila) as a test case because it is emerging as a powerful model system for studying the genetics of lipid metabolism but, due to its small size, it can be difficult to purify sufficient amounts of any one cell type to do conventional mass spectrometry.
The researchers used MIMS to monitor how growing Drosophila larvae metabolise a dietary lipid, palmitate. They were able to observe that a stable isotope tracer (13C), derived from 13C-labelled palmitate in the larval diet, becomes localized to tiny particles called lipid droplets inside cells of the intestine and adipose tissue. By varying the length of time that larvae were fed 13C-palmitate, it was possible to quantify the rates of 13C incorporation and turnover within an individual lipid droplet inside an intestinal versus adipose cell. These findings demonstrate the power of MIMS for imaging and quantitating lipid metabolism at the subcellular level.
MIMS has allowed us and Claude Lechene’s other collaborators to visualize and to quantitate several different aspects of metabolism with an impressive level of spatial resolution, exceeding that of a light microscope. We hope that these proof-of-principle studies will encourage other laboratories to use this, and related imaging mass spectrometry technologies, to address important biological and medical questions at the interface between metabolism and cell biology.
Alex Gould
Rapid lipid turnover in Drosophila intestinal cells after a13C-palmitate pulse-chase
Upper panels show 14N images-lipid droplets appear as dark circles. Lower panels show the corresponding 13C:12C hue saturation intensity images-showing that the high 13C signal in lipid droplets at 0-hr declines after a 4-hr dietary 12C-palmitate chase.
Original article
Matthew L. Steinhauser, Andrew P. Bailey, Samuel E. Senyo, Christelle Guillermier, Todd S. Perlstein, Alex P. Gould, Richard T. Lee & Claude P. Lechene (2012)
Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism
Nature epub ahead of print. Publisher abstract.
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