†Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
‡Department of Chemistry, Ben-Gurion University of the Negev, Be'er Sheva 84105, Israel.
ACS Nano. 2015;9(4):4085-95. doi: 10.1021/acsnano.5b00133. Epub 2015 Mar 30.
Phospholipid membranes could be considered a prime example of the ability of nature to produce complex yet ordered structures, by spontaneous and efficient self-assembly. Inspired by the unique properties and architecture of phospholipids, we designed simple amphiphilic decapeptides, intended to fold in the center of the peptide sequence, with a phosphorylated serine "head" located within a central turn segment, and two hydrophobic "tails". The molecular design also included the integration of the diphenylalanine motif, previously shown to facilitate self-assembly and increase nanostructure stability. Secondary structure analysis of the peptides indeed indicated the presence of stabilized conformations in solution, with a central turn connecting two hydrophobic "tails", and interactions between the hydrophobic strands. The mechanisms of assembly into supramolecular structures involved structural transitions between different morphologies, which occurred over several hours, leading to the formation of distinctive nanostructures, including half-elliptical nanosheets and curved tapes. The phosphopeptide building blocks appear to self-assemble via a particular combination of aromatic, hydrophobic and ionic interactions, as well as hydrogen bonding, as demonstrated by proposed constructed simulated models of the peptides and self-assembled nanostructures. Molecular dynamics simulations also gave insight into mechanisms of structural transitions of the nanostructures at a molecular level. Because of the biocompatibility of peptides, the phosphopeptide assemblies allow for expansion of the library of biomolecular nanostructures available for future design and application of biomedical devices.
磷脂膜可以被认为是自然界通过自发和高效的自组装产生复杂而有序结构的一个主要例子。受磷脂独特性质和结构的启发，我们设计了简单的两亲性十肽，旨在肽序列的中心折叠，带有一个位于中央环段内的磷酸化丝氨酸“头部”和两个疏水性“尾部”。分子设计还包括整合二苯丙氨酸基序，该基序先前被证明有助于自组装并提高纳米结构的稳定性。肽的二级结构分析确实表明在溶液中存在稳定的构象，其中中央环连接两个疏水性“尾部”，以及疏水链之间的相互作用。组装成超分子结构的机制涉及不同形态之间的结构转变，这些转变在几个小时内发生，导致形成独特的纳米结构，包括半椭圆形纳米片和弯曲的带子。磷肽构建块似乎通过特定的芳香族、疏水性和离子相互作用以及氢键的组合自组装，正如所提出的肽和自组装纳米结构的模拟模型所表明的那样。分子动力学模拟还深入了解了纳米结构在分子水平上的结构转变机制。由于肽的生物相容性，磷肽组装允许扩展可用的生物分子纳米结构库，以用于未来设计和应用生物医学设备。
