**1. Introduction**

Low density lipoproteins (LDLs) are the principal transporter of cholesterol and fat in human blood. Circulating LDLs guarantee a constant supply of cholesterol for tissues and cells, whereas cholesterol is required for membrane synthesis, modulation of membrane fluidity and the regulation of cell signaling pathways. The function of LDL in metabolism is mediating by cellular uptake via receptor-mediated endocytosis followed by lysosomal degradation [1,2], and is strongly dependent on the lipid distribution, the structure of LDL particles and on the proper conformational orientation of apolipoprotein B100 (apo-B100). Apo-B100 is the sole protein component of LDL being mainly located on the surface of LDL. Apart from their well established role as lipid transporter, LDL particles are intimately involved in the progression of cardiovascular diseases such as atherosclerosis or stroke, which are among the most prevalent causes of death in developed countries [3]. In particular, raised plasma levels of LDL are linked to an increased risk for disease. Moreover, dysregulations of LDL due to abnormalities in LDL structure have been identified as independent predictors of risk for coronary heart diseases [4,5]. LDL particles by themselves are highly heterogeneous in nature, varying in their buoyant densities, size, surface charge and chemical composition [6,7], and these biochemical characteristics determine the fate of LDL in the subendothelial space [8,9]. For example, small, dense LDL subclasses are more atherogenic than their light counterparts, which are more susceptible to modifications [5,10]. Modifications of LDL, primarily through oxidation, enzymatic degradation or lipolysis are the initiating factors in early atherosclerosis. In that case, LDL particles accumulate in the intima of the arterial wall where apo-B100 binds to proteoglycans of the extracellular matrix through ionic

<sup>© 2012</sup>Prassl and Laggner, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

interactions. As a consequence, LDL becomes trapped in the subendothelium, where it is prone to oxidation processes, aggregation and fusion. Bioactive lipids, such as oxidized phospholipids, lysolipids or oxidized cholesterylester, are released from LDL particles, which are simultaneously non-specifically altered. A broad spectrum of diverse LDL particles with non-defined physicochemical properties is generated that, in turn, promotes a rapid uptake of these particles by macrophages to form foam cells [11]. This is one of the key steps in the progression of atherosclerosis. Today, atherosclerosis is known to be a chronic inflammatory disorder of the blood vessels and recognized as a prevailing cause of cardiovascular disorders, the leading causes of morbidity and mortality worldwide [12]. Since the early initiation of atherosclerosis strongly depends on the metabolism of LDL, which is predominantly triggered by molecular characteristics of LDL, it is of paramount biomedical importance to explore structural features of LDL particles in great detail. However, mostly due to the complex nature of LDL particles many questions concerning molecular details are still unanswered.

This article will review our current knowledge on the structure and dynamics of LDL particles. In fact, several recent studies revealed that the molecular organisation and dynamics of LDL core lipids, in close relationship to the intrinsic dynamics of LDL surface components, control not only the metabolism of lipids in humans, but determine the role of LDL in the pathogenesis of cardiovascular diseases. In this article, we will give a short historical review on LDL structure and then present prevailing concepts on the selforganisation of LDL. Special emphasis will be paid to dynamic features of LDL particles. In particular, we will discuss the interplay between structure and dynamics in more detail. Finally, we will give an outlook to promising future strategies to clarify the molecular structural details of LDL and how to exploit LDL nanoparticles for medical needs.
