Low-density lipoproteins (LDL) are natural lipid transporter in human plasma whose chemically modified forms contribute to the progression of atherosclerosis and cardiovascular diseases accounting for a vast majority of deaths in westernized civilizations. For the development of new treatment strategies, it is important to have a detailed picture of LDL nanoparticles on a molecular basis. Through the combination of X-ray and neutron small-angle scattering (SAS) techniques with high hydrostatic pressure (HHP) this study describes structural features of normolipidemic, triglyceride-rich and oxidized forms of LDL. Due to the different scattering contrasts for X-rays and neutrons, information on the effects of HHP on the internal structure determined by lipid rearrangements and changes in particle shape becomes accessible. Independent pressure and temperature variations provoke a phase transition in the lipid core domain. With increasing pressure an inter-related anisotropic deformation and flattening of the particle are induced. All LDL nanoparticles maintain their structural integrity even at 3000 bar and show a reversible response toward pressure variations. The present work depicts the complementarity of pressure and temperature as independent thermodynamic parameters and introduces HHP as a tool to study molecular assembling and interaction processes in distinct lipoprotein particles in a nondestructive manner.

中文翻译：

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高静水压诱导低密度脂蛋白纳米颗粒中的脂质相变和分子重排

低密度脂蛋白（LDL）是人体血浆中的天然脂质转运蛋白，其化学修饰形式会导致动脉粥样硬化和心血管疾病的进展，而这些疾病是西方文明中绝大多数死亡的原因。为了开发新的治疗策略，在分子基础上获得 LDL 纳米粒子的详细图像非常重要。通过将 X 射线和中子小角散射 (SAS) 技术与高静水压 (HHP) 相结合，本研究描述了正常血脂、富含甘油三酯和氧化形式 LDL 的结构特征。由于 X 射线和中子的散射对比度不同，因此可以获取有关 HHP 对由脂质重排和颗粒形状变化决定的内部结构的影响的信息。独立的压力和温度变化引起脂质核心域的相变。随着压力的增加，引起相互关联的各向异性变形和颗粒的扁平化。所有 LDL 纳米颗粒即使在 3000 bar 的压力下也能保持其结构完整性，并对压力变化表现出可逆的响应。目前的工作将压力和温度的互补性描述为独立的热力学参数，并引入 HHP 作为以非破坏性方式研究不同脂蛋白颗粒中分子组装和相互作用过程的工具。