Golovina Elena A, Golovin Andrey V, Hoekstra Folkert A, Faller Roland
Wageningen NMR Center and Laboratory of Biophysics, Wageningen University, Wageningen, The Netherlands.
Biophys J. 2009 Jul 22;97(2):490-9. doi: 10.1016/j.bpj.2009.05.007.
According to the water replacement hypothesis, trehalose stabilizes dry membranes by preventing the decrease of spacing between membrane lipids under dehydration. In this study, we use molecular-dynamics simulations to investigate the influence of trehalose on the area per lipid (APL) and related structural properties of dehydrated bilayers in atomic detail. The starting conformation of a palmitoyloleolylphosphatidylcholine lipid bilayer in excess water was been obtained by self-assembly. A series of molecular-dynamics simulations of palmitoyloleolylphosphatidylcholine with different degrees of dehydration (28.5, 11.7, and 5.4 waters per lipid) and different molar trehalose/lipid ratios (<1:1, 1:1, and >1:1) were carried out in the NPT ensemble. Water removal causes the formation of multilamellar "stacks" through periodic boundary conditions. The headgroups reorient from pointing outward to inward with dehydration. This causes changes in the electrostatic interactions between interfaces, resulting in interface interpenetration. Interpenetration creates self-spacing of the bilayers and prevents gel-phase formation. At lower concentrations, trehalose does not separate the interfaces, and acting together with self-spacing, it causes a considerable increase of APL. APL decreases at higher trehalose concentrations when the layer of sugar physically separates the interfaces. When interfaces are separated, the model confirms the water replacement hypothesis.
根据水替代假说，海藻糖通过防止脱水过程中膜脂之间间距的减小来稳定干燥的膜。在本研究中，我们使用分子动力学模拟，从原子层面详细研究海藻糖对脱水双层膜中每个脂质的面积（APL）及相关结构性质的影响。通过自组装获得了过量水中棕榈酰油酰磷脂酰胆碱脂质双层的初始构象。在NPT系综中对不同脱水程度（每个脂质含28.5、11.7和5.4个水分子）和不同摩尔海藻糖/脂质比（<1:1、1:1和>1:1）的棕榈酰油酰磷脂酰胆碱进行了一系列分子动力学模拟。通过周期性边界条件，脱水导致形成多层“堆叠”结构。随着脱水，头基从向外指向转变为向内指向。这导致界面间静电相互作用发生变化，进而导致界面相互渗透。相互渗透产生了双层膜的自间距，并防止了凝胶相的形成。在较低浓度下，海藻糖不会分隔界面，而是与自间距共同作用，导致APL显著增加。当糖层在物理上分隔界面时，在较高海藻糖浓度下APL会降低。当界面被分隔时，该模型证实了水替代假说。
