A new way of visualizing the distribution of cholesterol in cells and tissues has been developed by researchers from UCLA and the University of Western Australia. Their research brings insights into the movement of cholesterol into and out of cells and could eventually establish mechanisms linking cholesterol to coronary artery disease.
The high-resolution imaging mass spectrometry approach, called NanoSIMS imaging, let the team visualize and quantify a pool of cholesterol called “accessible cholesterol” on the surface of cells.
Cholesterol, an important lipid, is critical for maintaining the integrity of the plasma membrane in every cell in the body. But elevated levels of cholesterol in the blood represent a risk factor for coronary artery disease.
The accessible pool of cholesterol on the plasma membrane is thought to play a role in regulating production of cholesterol by cells and likely plays a role in the ability of cells to unload surplus cholesterol. “Accessible cholesterol” on the surface of cells can be detected with a cholesterol-binding protein from bacteria.
By taking advantage of the bacterial protein, along with NanoSIMS imaging, researchers showed that the accessible pool of cholesterol is not evenly distributed on a cell’s plasma membrane but instead is highly enriched on specialized projections from the plasma membrane called microvilli.
Co-author Dr. Stephen Young, a distinguished professor of medicine and human genetics at the David Geffen School of Medicine at UCLA, said:
“In the past, other scientists had speculated that microvilli play a role in moving cholesterol into and out of cells. The discovery that ‘accessible cholesterol’ is highly enriched in microvilli lends support to that idea."
Dr. Haibo Jiang, a study co-author, noted that NanoSIMS imaging provides unique insights into cholesterol distribution on the plasma membrane and future studies will make it possible to assess mechanisms by which cells dispose of excess cholesterol.
“We would like to gain a better understanding of the mechanisms of cholesterol movement in cells and tissues,” said Jiang. “We believe that NanoSIMS imaging could yield new strategies for lowering cholesterol levels in the blood or at least new strategies for optimizing the effects of existing cholesterol-lowering drugs."
“The plan now is to use NanoSIMS, along with novel biochemical approaches, to investigate cholesterol distribution and movement in multiple cell types."
Cuiwen He, Xuchen Hu, Rachel S. Jung, Thomas A. Weston, Norma P. Sandoval, Peter Tontonoz, Matthew R. Kilburn, Loren G. Fong, Stephen G. Young, Haibo Jiang High-resolution imaging and quantification of plasma membrane cholesterol by NanoSIMS Proceedings of the National Academy of Sciences, 2017; 114 (8): 2000 DOI: 10.1073/pnas.1621432114
Image: NanoSIMS imaging of “accessible cholesterol” on cultured cells, showing accessible cholesterol on the microvilli projections from cells. Credit: Haibo Jiang and Stephen Young