Mechanical and crystallographic analysis of cholesterol crystals puncturing biological membranes

Ischemic heart disease often leads to myocardial infarction and remains the most common cause for death in humans. Although the exact impetus for the infarction remains elusive, a mechanism has been proposed that relates the disease to the observed high cholesterol levels in the body. The mechanism claims that cholesterol crystallizes inside the arterial plaque into needle‐shaped crystals. The crystals puncture the fibrous cap of the plaque, whereby the necrotic contents of the plaque are spilled, subsequently clotting the blood vessels. This hypothesis has not been given sufficient attention partly due to the purported softness of the organic crystals and the common platy habit of the known crystal forms of cholesterol. In this work it is shown that, from hydrophobic solutions that attempt to emulate the plaque contents, a new solid form of cholesterol crystallizes as prisms with mucronate tips, and they are sufficiently strong to puncture a lamb pericardium, which mimics the plaque cap. The properties of the crystals were assessed by mechanical, structural, and crystallographic analyses. The results support the hypothesis that the cholesterol crystals can be considered, at least within the framework of the proposed mechanism, a possible cause of myocardial infarction.