Lewis R N, McElhaney R N, Harper P E, Turner D C, Gruner S M
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Biophys J. 1994 Apr;66(4):1088-103. doi: 10.1016/S0006-3495(94)80890-2.
We have synthesized a number of 1,2-diacyl phosphatidylcholines with hydrophobic substituents adjacent to the carbonyl group of the fatty acyl chain and studied their thermotropic phase behavior by differential scanning calorimetry, 31P-nuclear magnetic resonance spectroscopy, and x-ray diffraction. Our results indicate that the hydrocarbon chain-melting phase transition temperatures of these lipids are lower than those of the n-saturated diacylphosphatidylcholines of similar chain length. In the gel phase, the 2-alkyl substituents on the fatty acyl chains seem to inhibit the formation of tightly packed, partially dehydrated, quasi-crystalline bilayers (Lc phases), although possibly promoting the formation of chain-interdigitated bilayers. In the liquid-crystalline state, however, these 2-alkyl substituents destabilize the lamellar phase with respect to one or more inverted nonlamellar structures. In general, increases in the length, bulk, or rigidity of the alkyl substituent result in an increased destabilization of the lamellar gel and liquid-crystalline phases and a greater tendency to form inverted nonlamellar phases, the nature of which depends upon the size of the 2-alkyl substituent. Unlike normal non-lamella-forming lipids such as the phosphatidylethanolamines, increases in the length of the main acyl chain stabilize the lamellar phases and reduce the tendency to form nonlamellar structures. Our results establish that with a judicious choice of a 2-alkyl substituent and hydrocarbon chain length, phosphatidylcholines (and probably most other so-called "bilayer-preferring" lipids) can be induced to form a range of inverted nonlamellar structures at relatively low temperatures. The ability to vary the lamellar/nonlamellar phase preference of such lipids should be useful in studies of bilayer/nonbilayer phase transitions and of the molecular organization of various nonlamellar phases. Moreover, because the nonlamellar phases can easily be induced at physiologically relevant temperatures and hydration levels while avoiding changes in polar headgroup composition, this new class of 2-alkyl-substituted phosphatidylcholines should prove valuable in studies of the physiological role of non-lamella-forming lipids in reconstituted lipid-protein model membranes.
我们合成了多种在脂肪酰链羰基相邻位置带有疏水取代基的1,2 - 二酰基磷脂酰胆碱，并通过差示扫描量热法、³¹P - 核磁共振光谱法和X射线衍射研究了它们的热致相行为。我们的结果表明，这些脂质的烃链熔化相变温度低于类似链长的正饱和二酰基磷脂酰胆碱。在凝胶相中，脂肪酰链上的2 - 烷基取代基似乎抑制了紧密堆积、部分脱水的准晶态双层膜（Lc相）的形成，尽管可能促进了链相互交错的双层膜的形成。然而，在液晶态下，相对于一种或多种反相非层状结构，这些2 - 烷基取代基会使层状相不稳定。一般来说，烷基取代基的长度、体积或刚性增加会导致层状凝胶相和液晶相的不稳定增加，以及形成反相非层状相的倾向更大，反相非层状相的性质取决于2 - 烷基取代基的大小。与正常的非层状形成脂质如磷脂酰乙醇胺不同，主酰链长度的增加会稳定层状相并降低形成非层状结构的倾向。我们的结果表明，通过明智地选择2 - 烷基取代基和烃链长度，可以诱导磷脂酰胆碱（可能还有大多数其他所谓的“双层偏好”脂质）在相对较低的温度下形成一系列反相非层状结构。改变此类脂质的层状/非层状相偏好的能力在双层/非双层相变以及各种非层状相的分子组织研究中应该是有用的。此外，由于在生理相关温度和水合水平下可以很容易地诱导非层状相，同时避免极性头部基团组成的变化，这种新型的2 - 烷基取代磷脂酰胆碱在研究重组脂质 - 蛋白质模型膜中形成非层状脂质的生理作用方面应该被证明是有价值的。
