Harroun T A, Heller W T, Weiss T M, Yang L, Huang H W
Physics Department, Rice University, Houston, Texas 77251, USA.
Biophys J. 1999 Jun;76(6):3176-85. doi: 10.1016/S0006-3495(99)77469-2.
We present a quantitative analysis of the effects of hydrophobic matching and membrane-mediated protein-protein interactions exhibited by gramicidin embedded in dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLPC) bilayers (Harroun et al., 1999. Biophys. J. 76:937-945). Incorporating gramicidin, at 1:10 peptide/lipid molar ratio, decreases the phosphate-to-phosphate (PtP) peak separation in the DMPC bilayer from 35.3 A without gramicidin to 32.7 A. In contrast, the same molar ratio of gramicidin in DLPC increases the PtP from 30.8 A to 32.1 A. Concurrently, x-ray in-plane scattering showed that the most probable nearest-neighbor separation between gramicidin channels was 26.8 A in DLPC, but reduced to 23.3 A in DMPC. In this paper we review the idea of hydrophobic matching in which the lipid bilayer deforms to match the hydrophobic surface of the embedded proteins. We use a simple elasticity theory, including thickness compression, tension, and splay terms to describe the membrane deformation. The energy of membrane deformation is compared with the energy cost of hydrophobic mismatch. We discuss the boundary conditions between a gramicidin channel and the lipid bilayer. We used a numerical method to solve the problem of membrane deformation profile in the presence of a high density of gramicidin channels and ran computer simulations of 81 gramicidin channels to find the equilibrium distributions of the channels in the plane of the bilayer. The simulations contain four parameters: bilayer thickness compressibility 1/B, bilayer bending rigidity Kc, the channel-bilayer mismatch Do, and the slope of the interface at the lipid-protein boundary s. B, Kc, and Do were experimentally measured; the only free parameter is s. The value of s is determined by the requirement that the theory produces the experimental values of bilayer thinning by gramicidin and the shift in the peak position of the in-plane scattering due to membrane-mediated channel-channel interactions. We show that both hydrophobic matching and membrane-mediated interactions can be understood by the simple elasticity theory.
我们对嵌入二肉豆蔻酰磷脂酰胆碱（DMPC）和二月桂酰磷脂酰胆碱（DLPC）双层膜中的短杆菌肽所表现出的疏水匹配效应和膜介导的蛋白质-蛋白质相互作用进行了定量分析（Harroun等人，1999年。《生物物理杂志》76:937 - 945）。以肽/脂质摩尔比1:10掺入短杆菌肽，会使DMPC双层膜中磷酸根到磷酸根（PtP）峰间距从无短杆菌肽时的35.3 Å减小到32.7 Å。相比之下，相同摩尔比的短杆菌肽在DLPC中会使PtP从30.8 Å增加到32.1 Å。同时，X射线面内散射表明，短杆菌肽通道之间最可能的最近邻间距在DLPC中为26.8 Å，但在DMPC中减小到23.3 Å。在本文中，我们回顾了疏水匹配的概念，即脂质双层膜会变形以匹配嵌入蛋白质 的疏水表面。我们使用一种简单的弹性理论，包括厚度压缩、张力和展布项来描述膜的变形。将膜变形的能量与疏水不匹配的能量成本进行比较。我们讨论了短杆菌肽通道与脂质双层膜之间的边界条件。我们使用数值方法解决了在高密度短杆菌肽通道存在下膜变形轮廓的问题，并对81个短杆菌肽通道进行了计算机模拟，以找到通道在双层膜平面内的平衡分布。模拟包含四个参数：双层膜厚度压缩性1/B、双层膜弯曲刚度Kc、通道 - 双层膜不匹配度Do以及脂质 - 蛋白质边界处界面的斜率s。B、Kc和Do是通过实验测量的；唯一的自由参数是s。s的值由该理论产生短杆菌肽导致的双层膜变薄的实验值以及由于膜介导的通道 - 通道相互作用引起的面内散射峰位置的移动这一要求来确定。我们表明，疏水匹配和膜介导的相互作用都可以通过简单的弹性理论来理解。
