Translocation Mechanism(s) of Cell-Penetrating Peptides: Biophysical Studies Using Artificial Membrane Bilayers
Translocation Mechanism(s) of Cell-Penetrating Peptides: Biophysical Studies Using Artificial Membrane Bilayers
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DOI：
10.1021/bi501392n
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发表时间：
2015-01-20
期刊：
影响因子：
2.9
通讯作者：
Swiecicki, Jean-Marie
中科院分区：
文献类型：
--
作者：
Di Pisa, Margherita;Chassaing, Gerard;Swiecicki, Jean-Marie
细胞穿透肽（CPPs）跨越细胞膜的能力已经在将生物活性化合物递送到活细胞的细胞质中得到了许多应用。它们的内化机制多次受到质疑，经过20年的激烈辩论，现在人们广泛接受能量依赖和能量独立机制都可以解释它们的渗透特性。然而，不依赖于细胞内化机制而发生的能量独立机制，即直接易位，仍有待在分子水平上充分合理化。利用人工膜双层，最近在理解直接易位事件方面取得了进展。这篇综述总结了我们目前对转运过程的理解，从CPP在膜上的吸附到膜本身的交叉。我们描述了发生在直接易位之前的不同关键步骤，因为每个步骤都可以促进和/或阻碍CPP通过膜的易位。然后，我们剖析了CPPs的存在对膜的修饰。最后，我们重点介绍了描述直接易位机制的最新研究。这些结果提供了一个重要的框架，在其中设计新的CPPs和合理化CPPs在其穿透能力的最终选择性。
The ability of cell-penetrating peptides (CPPs) to cross cell membranes has found numerous applications in the delivery of bioactive compounds to the cytosol of living cells. Their internalization mechanisms have been questioned many times, and after 20 years of intense debate, it is now widely accepted that both energy-dependent and energy-independent mechanisms account for their penetration properties. However, the energy-independent mechanisms, named direct translocation, occurring without the requirement of the cell internalization machinery, remain to be fully rationalized at the molecular level. Using artificial membrane bilayers, recent progress has been made toward the comprehension of the direct translocation event. This review summarizes our current understanding of the translocation process, starting from the adsorption of the CPP on the membrane to the membrane crossing itself. We describe the different key steps occurring before direct translocation, because each of them can promote and/or hamper translocation of the CPP through the membrane. We then dissect the modification to the membranes induced by the presence of the CPPs. Finally, we focus on the latest studies describing the direct translocation mechanisms. These results provide an important framework within which to design new CPPs and to rationalize an eventual selectivity of CPPs in their penetration ability.