Assessment of the nano-mechanical properties of healthy and atherosclerotic coronary arteries by atomic force microscopy

• DOI: 10.1098/rsif.2023.0674
• Publication Date: 2024-02-07T00:05:36Z
• Authors: Fotios Savvopoulos; Michael C. Keeling; Daniele Carassiti; Nicholas A. Fogell; Miten B. Patel; Jarka Naser; Núria Gavara; Ranil de Silva; Rob Krams
• Keywords: 0301 basic medicine; collagen microstructure; nano-indentation; Microscopy; atomic force microscopy; Atomic Force; Coronary Artery Disease; mechanical properties; Lipids; 03 medical and health sciences; Elastic Modulus; Humans; Collagen; atherosclerosis; coronary arteries; Life Sciences–Engineering interface; Retrospective Studies; Plaque; Atherosclerotic

Nano-indentation techniques might be better equipped to assess the heterogeneous material properties of plaques than macroscopic methods but there are no bespoke protocols for this kind of material testing for coronary arteries. Therefore, we developed a measurement protocol to extract mechanical properties from healthy and atherosclerotic coronary artery tissue sections. Young's modulus was derived from force-indentation data. Metrics of collagen fibre density were extracted from the same tissue, and the local material properties were co-registered to the local collagen microstructure with a robust framework. The locations of the indentation were retrospectively classified by histological category (healthy, plaque, lipid-rich, fibrous cap) according to Picrosirius Red stain and adjacent Hematoxylin & Eosin and Oil-Red-O stains. Plaque tissue was softer ( p < 0.001) than the healthy coronary wall. Areas rich in collagen within the plaque (fibrous cap) were significantly ( p < 0.001) stiffer than areas poor in collagen/lipid-rich, but less than half as stiff as the healthy coronary media. Young's moduli correlated (Pearson's ρ = 0.53, p < 0.05) with collagen content. Atomic force microscopy (AFM) is capable of detecting tissue stiffness changes related to collagen density in healthy and diseased cardiovascular tissue. Mechanical characterization of atherosclerotic plaques with nano-indentation techniques could refine constitutive models for computational modelling.