Lipoprotein Particles Interact with Membranes and Transfer Their Cargo without Receptors,Biochemistry

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Lipoprotein Particles Interact with Membranes and Transfer Their Cargo without Receptors
Biochemistry ( IF 2.9 ) Pub Date : 2020-11-04 , DOI: 10.1021/acs.biochem.0c00748
Birgit Plochberger _{1,

2,

3} , Taras Sych ₄ , Florian Weber _{3,

4} , Jiri Novacek ₅ , Markus Axmann ₆ , Herbert Stangl ₆ , Erdinc Sezgin _{4,

7}

Affiliation

Lipid transfer from lipoprotein particles to cells is essential for lipid homeostasis. High-density lipoprotein (HDL) particles are mainly captured by cell membrane-associated scavenger receptor class B type 1 (SR-B1) from the bloodstream, while low-density and very-low-density lipoprotein (LDL and VLDL, respectively) particles are mostly taken up by receptor-mediated endocytosis. However, the role of the target lipid membrane itself in the transfer process has been largely neglected so far. Here, we study how lipoprotein particles (HDL, LDL, and VLDL) interact with synthetic lipid bilayers and cell-derived membranes and transfer their cargo subsequently. Employing cryo-electron microscopy, spectral imaging, and fluorescence (cross) correlation spectroscopy allowed us to observe integration of all major types of lipoprotein particles into the membrane and delivery of their cargo in a receptor-independent manner. Importantly, the biophysical properties of the target cell membranes change upon delivery of cargo. The concept of receptor-independent interaction of lipoprotein particles with membranes helps us to better understand lipoprotein particle biology and can be exploited for novel treatments of dyslipidemia diseases.

中文翻译：

脂蛋白颗粒与膜相互作用并在没有受体的情况下转移其货物

从脂蛋白颗粒到细胞的脂质转移对于脂质稳态至关重要。高密度脂蛋白 (HDL) 颗粒主要被血流中的细胞膜相关清除受体 B 型 1 (SR-B1) 捕获，而低密度和极低密度脂蛋白（分别为 LDL 和 VLDL）颗粒主要由受体介导的内吞作用吸收。然而，迄今为止，靶脂质膜本身在转移过程中的作用在很大程度上被忽视了。在这里，我们研究脂蛋白颗粒（HDL、LDL 和 VLDL）如何与合成的脂质双层和细胞衍生膜相互作用并随后转移它们的货物。采用低温电子显微镜，光谱成像，和荧光（交叉）相关光谱使我们能够观察到所有主要类型的脂蛋白颗粒整合到膜中并以不依赖受体的方式递送它们的货物。重要的是，目标细胞膜的生物物理特性在货物交付时发生变化。脂蛋白颗粒与膜的受体非依赖性相互作用的概念有助于我们更好地了解脂蛋白颗粒生物学，并可用于治疗血脂异常疾病。

更新日期：2020-11-17

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