Papahadjopoulos D, Vail W J, Pangborn W A, Poste G
Biochim Biophys Acta. 1976 Oct 5;448(2):265-83. doi: 10.1016/0005-2736(76)90241-8.
The effect of divalent metals on the interaction and mixing of membrane components in vesicles prepared from acidic phospholipids has been examined using freeze-fracture electron microscopy and differential scanning calorimetry. Ca2+, and to a certain extent Mg2+, induce extensive mixing of vesicle membrane components and drastic structural rearrangements to form new membranous structures. In contrast to the mixing of vesicle membrane components in the absence of Ca2+ described in the accompanying paper which occurs via diffusion of lipid molecules between vesicles, mixing of membrane components induced by Ca2+ or Mg2+ results from true fusion of entire vesicles. There appears to be a "threshold" concentration at which Ca2+ and Mg2+ become effective in inducing vesicle fusion and the threshold concentration varies for different acidic phospholipid species. Different phospholipids also vary markedly in their relative responsiveness to Ca2+ and Mg2+, with certain phospholipids being much more susceptible to fusion by Ca2+ than Mg2+. Vesicle fusion induced by divalent cations also requires that the lipids of the interacting membranes be in a "fluid" state (T greater than Tc). Fusion of vesicle membranes by Ca2+ and Mg2+ does not appear to be due to simple electrostatic charge neutralization. Rather the action of these cations in inducing fusion is related to their ability to induce isothermal phase transitions and phase separations in phospholipid membranes. It is suggested that under these conditions membranes become transiently susceptible to fusion as a result of changes in molecular packing and creation of new phase boundaries induced by Ca2+ (or Mg2+).
利用冷冻断裂电子显微镜和差示扫描量热法，研究了二价金属对由酸性磷脂制备的囊泡中膜成分相互作用和混合的影响。Ca2+，以及在一定程度上Mg2+，可诱导囊泡膜成分的广泛混合和剧烈的结构重排，从而形成新的膜结构。与随附论文中描述的在没有Ca2+的情况下囊泡膜成分的混合（通过脂质分子在囊泡之间的扩散发生）相反，由Ca2+或Mg2+诱导的膜成分混合是整个囊泡真正融合的结果。似乎存在一个“阈值”浓度，在该浓度下Ca2+和Mg2+在诱导囊泡融合方面变得有效，并且不同酸性磷脂种类的阈值浓度有所不同。不同的磷脂对Ca2+和Mg2+的相对反应性也有显著差异，某些磷脂对Ca2+诱导的融合比Mg2+更敏感。二价阳离子诱导的囊泡融合还要求相互作用膜的脂质处于“流体”状态（T大于Tc）。Ca2+和Mg2+诱导的囊泡膜融合似乎不是由于简单的静电荷中和。相反，这些阳离子在诱导融合中的作用与其在磷脂膜中诱导等温相变和相分离的能力有关。有人提出，在这些条件下，由于Ca2+（或Mg2+）诱导的分子堆积变化和新相界的产生，膜会暂时易于融合。
