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Neta Varsano1, Xueting Jin2, Tali Dadosh1, Nadav Elad1, Eva Pereiro3, Ana J Perez-Berna3, Fabio Beghi1, Howard S. Kruth2, Leslie Leiserowitz1, and Lia Addadi1 (1Weizmann Institute of Science, Israel. 2National Institutes of Health, , MD,USA 3ALBA Synchrotron Light Source, Spain )
Accumulation of cholesterol in artery walls is a prominent feature of atherosclerosis, a major precursor of most cardiovascular diseases. Cholesterol crystal deposition is a crucial stage in the disease involving cell death, increased inflammatory response and plaque disruption. Herein we aim to elucidate cholesterol crystal formation in 3D and at high resolution. For studying the early stages of cholesterol segregation in cell culture, we incubated macrophage cells with acLDL particles for different time lengths and followed the cholesterol segregation process by using an antibody that identifies the newly formed cholesterol crystals. Direct imaging of the cells was achieved by using a new correlative method that combines cryo SXT with STORM. At early incubation times, we identified small rhomb crystals (200−400 nm) associated with cell plasma membranes. After longer incubation times, large rod-like crystals (~10 µm) with a different structure of cholesterol grew at intracellular locations, indicating that the cell membrane environment determines the crystal form. We believe that our findings provide new insight into pathological cholesterol crystal formation and processing.https://scholar.google.com/citations?hl=en&user=kNwFtEUAAAAJ&view_op=list_works&sortby=pubdate