Dynamic AFM detection of the oxidation-induced changes in size, stiffness, and stickiness of low-density lipoprotein

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Journal of Nanobiotechnology Open Access

Dynamic AFM detection of the oxidation‑induced changes in size, stiffness, and stickiness of low‑density lipoprotein Kun Wang1,2, Yuanfang Li1,2, Chao Luo2 and Yong Chen2* 

Abstract  Background:  Low-density lipoprotein (LDL) is an important plasma lipoprotein transporting lipids to peripheral tissues/cells. The oxidation of LDL plays critical roles in atherogenesis and its oxidized form (oxLDL) is an important risk factor of atherosclerosis. The biomechanical properties of LDL/oxLDL are closely correlated with the disease. To date, however, the oxidation-induced changes in size and biomechanical properties (stiffness and stickiness) of LDL particles are less investigated. Methods:  In this study, copper-induced LDL oxidation was confirmed by detecting electrophoretic mobility, malondialdehyde production, and conjugated diene formation. Then, the topographical and biomechanical mappings of LDL particles before/after and during oxidation were performed by using atomic force microscopy (AFM) and the size and biomechanical forces of particles were measured and quantitatively analyzed. Results:  Oxidation induced a significant decrease in size and stiffness (Young’s modulus) but a significant increase in stickiness (adhesion force) of LDL particles. The smaller, softer, and stickier characteristics of oxidized LDL (oxLDL) partially explains its pro-atherosclerotic role. Conclusions:  The data implies that LDL oxidation probably aggravates atherogenesis by changing the size and biomechanical properties of LDL particles. The data may provide important information for a better understanding of LDL/oxLDL and atherosclerosis. Keywords:  Low-density lipoprotein (LDL), Atherosclerosis, Atomic force microscopy (AFM), LDL oxidation, Young’s modulus, Adhesion force Background Low-density lipoprotein (LDL) is one of the five lipidtransporting plasma lipoproteins in human blood circulation. The elevated level of LDL-cholesterol (LDL-C) has been regarded as a major risk factor of atherosclerosis which is a chronic cardiovascular disease characterized *Correspondence: [email protected]; [email protected] 2 School of Materials Science and Engineering, Nanchang University, 999 Xuefu Ave., Honggutan District, Nanchang 330031, Jiangxi, P. R. China Full list of author information is available at the end of the article

by the formation of atherosclerotic plaques and subsequently the narrowing of arterial lumens and is one of the leading causes of death and disability worldwide [1, 2]. The oxidized form of LDL (oxLDL) plays a critical role in the initiation and sustainability of atherogenesis by triggering lipid deposition/accumulation in cells (particularly macrophages) in the subendothelial space (i.e. the intima layer of arterial wall) [3, 4]. We hypothesized that LDL oxidation may also change the physical properties (e.g.

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