Lee Ming-Tao, Hung Wei-Chin, Chen Fang-Yu, Huang Huey W
National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.
Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5087-92. doi: 10.1073/pnas.0710625105. Epub 2008 Mar 28.
How antimicrobial peptides form pores in membranes is of interest as a fundamental membrane process. However, the underlying molecular mechanism, which has potential applications in therapeutics, nonviral gene transfer, and drug delivery, has been in dispute. We have resolved this mechanism by observing the time-dependent process of pore formation in individual giant unilamellar vesicles (GUVs) exposed to a melittin solution. An individual GUV first expanded its surface area at constant volume and then suddenly reversed to expanding its volume at constant area. The area expansion, the volume expansion, and the point of reversal all match the results of equilibrium measurements performed on peptide-lipid mixtures. The mechanism includes a negative feedback that makes peptide-induced pores stable with a well defined size, contrary to the suggestion that peptides disintegrate the membrane in a detergent-like manner.
抗菌肽如何在膜上形成孔作为一种基本的膜过程备受关注。然而，其潜在应用于治疗、非病毒基因传递和药物递送的潜在分子机制一直存在争议。我们通过观察暴露于蜂毒肽溶液的单个巨型单层囊泡（GUV）中孔形成的时间依赖性过程，解决了这一机制。单个GUV首先在恒定体积下扩大其表面积，然后突然反转，在恒定面积下扩大其体积。面积扩大、体积扩大以及反转点均与对肽 - 脂质混合物进行的平衡测量结果相符。该机制包括一种负反馈，使得肽诱导的孔以明确的大小稳定存在，这与肽以类似洗涤剂的方式使膜解体的观点相反。
