Kerek Evan M, Prenner Elmar J
Department of Biological Sciences, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
Department of Biological Sciences, University of Calgary, Calgary, Alberta, T2N 1N4, Canada.
Biochim Biophys Acta. 2016 Dec;1858(12):3169-3181. doi: 10.1016/j.bbamem.2016.10.005. Epub 2016 Oct 11.
Following intake and absorption of Cd into the bloodstream, one possible target is the lipid membrane surrounding erythrocytes as well as kidney and liver cells where Cd accumulates. We investigated the interactions of Cd with model membranes from a biophysical perspective by using fluorescence spectroscopy and dynamic light scattering to monitor changes in liposome size, membrane fluidity and lipid phase transition. The fluorescent probe Laurdan was incorporated into liposomes and used to quantitate cadmium induced fluidity changes in model systems hydrated in 20mM HEPES, 100mM NaCl pH7.4. The metal effects on membranes composed of the zwitterionic phosphatidylcholine were compared to the negatively charged lipids phosphatidic acid (PA), cardiolipin (CL), phosphatidylglycerol (PG), phosphatidylserine (PS) and phosphatidylinositol (PI). The data showed that 5-2000μM Cd electrostatically targeted negatively charged lipids and increased the rigidity of these membranes whereby the gel to liquid crystalline phase of fully saturated anionic lipids was increased following the order: PG>PS>CL~PA. In addition, dynamic light scattering showed that Cd induced liposome aggregation in all negatively charged systems except for the PGs. Moreover, both effects were much stronger for saturated acyl chains versus unsaturated species. Finally, charge localization was important as lipids carrying the charge more distant from the hydrophobic core of the bilayer showed stronger interactions with Cd.
镉进入血液并被吸收后，一个可能的作用靶点是红细胞以及镉会在其中蓄积的肾和肝细胞周围的脂质膜。我们从生物物理学角度研究了镉与模型膜的相互作用，通过荧光光谱法和动态光散射来监测脂质体大小、膜流动性和脂质相变的变化。将荧光探针劳丹素掺入脂质体中，并用于定量镉在20mM HEPES、100mM NaCl pH7.4水合的模型系统中诱导的流动性变化。将金属对由两性离子磷脂酰胆碱组成的膜的影响与带负电荷的脂质磷脂酸（PA）、心磷脂（CL）、磷脂酰甘油（PG）、磷脂酰丝氨酸（PS）和磷脂酰肌醇（PI）进行了比较。数据表明，5 - 2000μM的镉以静电方式靶向带负电荷的脂质，并增加了这些膜的刚性，由此完全饱和的阴离子脂质从凝胶相到液晶相的转变增强，顺序为：PG>PS>CL~PA。此外，动态光散射表明，镉在除PGs之外的所有带负电荷的系统中均诱导脂质体聚集。而且，对于饱和酰基链而言，这两种效应比不饱和酰基链要强得多。最后，电荷定位很重要，因为携带电荷离双层疏水核心更远的脂质与镉的相互作用更强。
