Sule Kevin, Prenner Elmar J
Department of Biological Sciences, University of Calgary, Calgary, AB, T2N 1N4, Canada.
Eur Biophys J. 2022 Apr;51(3):205-223. doi: 10.1007/s00249-022-01589-x. Epub 2022 Feb 15.
Metal ion-membrane interactions have gained appreciable attention over the years resulting in increasing investigations into the mode of action of toxic and essential metals. More work has focused on essential ions like Ca or Mg and toxic metals like Cd and Pb, whereas this study investigates the effects of the abundant essential trace metal manganese with model lipid systems by screening zwitterionic and anionic glycerophospholipids. Despite its essentiality, deleterious impact towards cell survival is known under Mn stress. The fluorescent dyes Laurdan and diphenylhexatriene were used to assess changes in membrane fluidity both in the head group and hydrophobic core region of the membrane, respectively. Mn-rigidified membranes composed of the anionic phospholipids, phosphatidic acid, phosphatidylglycerol, cardiolipin, and phosphatidylserine. Strong binding resulted in large shifts of the phase transition temperature. The increase was in the order phosphatidylserine > phosphatidylglycerol > cardiolipin, and in all cases, saturated analogues > mono-unsaturated forms. Dynamic light scattering measurements revealed that Mn caused extensive aggregation of liposomes composed of saturated analogues of phosphatidic acid and phosphatidylserine, whilst the mono-unsaturated analogue had significant membrane swelling. Increased membrane rigidity may interfere with permeability of ions and small molecules, possibly disrupting cellular homeostasis. Moreover, liposome size changes could indicate fusion, which could also be detrimental to cellular transport. Overall, this study provided further understanding into the effects of Mn with biomembranes, whereby the altered membrane properties are consequential to the proper structural and signalling functions of membrane lipids.
多年来,金属离子与膜的相互作用受到了广泛关注,对有毒金属和必需金属的作用方式的研究也日益增多。更多的研究集中在钙或镁等必需离子以及镉和铅等有毒金属上,而本研究通过筛选两性离子和阴离子甘油磷脂,研究了丰富的必需微量元素锰对模型脂质体系的影响。尽管锰是必需的,但在锰胁迫下,它对细胞存活具有有害影响。荧光染料劳丹和二苯基己三烯分别用于评估膜头部基团和疏水核心区域的膜流动性变化。锰使由阴离子磷脂、磷脂酸、磷脂酰甘油、心磷脂和磷脂酰丝氨酸组成的膜变硬。强烈的结合导致相变温度大幅变化。增加的顺序为磷脂酰丝氨酸>磷脂酰甘油>心磷脂,在所有情况下,饱和类似物>单不饱和形式。动态光散射测量表明,锰导致由磷脂酸和磷脂酰丝氨酸的饱和类似物组成的脂质体大量聚集,而单不饱和类似物则有明显的膜肿胀。膜刚性增加可能会干扰离子和小分子的通透性,可能破坏细胞内稳态。此外,脂质体大小的变化可能表明融合,这也可能对细胞运输有害。总的来说,这项研究进一步了解了锰对生物膜的影响,由此改变的膜特性对膜脂的正确结构和信号功能至关重要。