TU Wien, Institute of Applied Physics, Vienna 1040, Austria.
Johannes Kepler University Linz, Institute of Biophysics, Linz 4020, Austria.
Biochemistry. 2020 Nov 17;59(45):4421-4428. doi: 10.1021/acs.biochem.0c00748. Epub 2020 Nov 4.
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.
脂蛋白颗粒向细胞内的脂质转移对于脂质稳态至关重要。高密度脂蛋白(HDL)颗粒主要通过细胞膜相关的清道夫受体 B 型 1(SR-B1)从血液中被捕获,而低密度脂蛋白(LDL)和极低密度脂蛋白(VLDL)颗粒则主要通过受体介导的内吞作用被摄取。然而,到目前为止,目标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,我们研究了脂蛋白颗粒(HDL、LDL 和 VLDL)如何与合成脂质双层和细胞衍生的膜相互作用,并随后传递其货物。通过使用冷冻电子显微镜、光谱成像和荧光(交叉)相关光谱学,我们能够观察到所有主要类型的脂蛋白颗粒整合到膜中,并以受体非依赖的方式传递其货物。重要的是,在货物传递后,靶细胞膜的生物物理性质发生了变化。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理解脂蛋白颗粒的生物学,并可用于治疗血脂异常疾病的新方法。
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