Simon S A, McIntosh T J, Magid A D, Needham D
Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710.
Biophys J. 1992 Mar;61(3):786-99. doi: 10.1016/S0006-3495(92)81883-0.
The effects of the cholesterol analog 5 alpha-cholestan-3 beta-ol-6-one (6-ketocholestanol) on bilayer structure, bilayer cohesive properties, and interbilayer repulsive pressures have been studied by a combination of x-ray diffraction, pipette aspiration, and dipole potential experiments. It is found that 6-ketocholestanol, which has a similar structure to cholesterol except with a keto moiety at the 6 position of the B ring, has quite different effects than cholesterol on bilayer organization and cohesive properties. Unlike cholesterol, 6-ketocholestanol does not appreciably modify the thickness of liquid-crystalline egg phosphatidylcholine (EPC) bilayers, and causes a much smaller increase in bilayer compressibility modulus than does cholesterol. These data imply that 6-ketocholestanol has both its hydroxyl and keto moieties situated near the water-hydrocarbon interface, thus making its orientation in the bilayer different from cholesterol's. The addition of equimolar 6-ketocholestanol into EPC bilayers increases the magnitude, but not the decay length, of the exponentially decaying repulsive hydration pressure between adjacent bilayers. Incorporation of equimolar 6-ketocholestanol into EPC monolayers increases the dipole potential by approximately 300 mV. These data are consistent with our previous observation that the magnitude of the hydration pressure is proportional to the square of the dipole potential. These results mean that 6-ketocholestanol, despite its location in the bilayer hydrocarbon region, approximately 10 A from the physical edge of the bilayer, modifies the organization of interlamellar water. We argue that the incorporation of 6-ketocholestanol into EPC bilayers increases the hydration pressure, at least in part, by increasing the electric field strength in the polar head group region.
通过X射线衍射、微量移液管抽吸和偶极电势实验相结合的方法，研究了胆固醇类似物5α-胆甾烷-3β-醇-6-酮（6-酮胆甾醇）对双层结构、双层内聚性质和双层间排斥压力的影响。研究发现，6-酮胆甾醇与胆固醇结构相似，只是在B环的6位有一个酮基部分，但其对双层组织和内聚性质的影响与胆固醇有很大不同。与胆固醇不同，6-酮胆甾醇不会明显改变液晶态鸡蛋卵磷脂（EPC）双层的厚度，并且与胆固醇相比，其导致双层压缩模量的增加要小得多。这些数据表明，6-酮胆甾醇的羟基和酮基部分都位于水-烃界面附近，因此其在双层中的取向与胆固醇不同。向EPC双层中加入等摩尔的6-酮胆甾醇会增加相邻双层之间指数衰减的排斥水合压力的大小，但不会增加其衰减长度。将等摩尔的6-酮胆甾醇掺入EPC单层中会使偶极电势增加约300 mV。这些数据与我们之前的观察结果一致，即水合压力的大小与偶极电势的平方成正比。这些结果意味着，6-酮胆甾醇尽管位于双层烃区域，距离双层的物理边缘约10埃，但会改变层间水的组织。我们认为，将6-酮胆甾醇掺入EPC双层中至少部分地通过增加极性头部基团区域的电场强度来增加水合压力。
