Self-Assembling Micelles Based on an Intrinsically Disordered Protein Domain
Self-Assembling Micelles Based on an Intrinsically Disordered Protein Domain
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DOI：
10.1021/jacs.8b10688
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发表时间：
2019-03-13
影响因子：
15
通讯作者：
Francis, Matthew B.
中科院分区：
文献类型：
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作者：
Klass, Sarah H.;Smith, Matthew J.;Francis, Matthew B.
含有亲水性和疏水性结构域的二嵌段聚合物的胶束结构的自组装对于药物和其他疏水性分子的封装引起了极大的兴趣。虽然大多数商业使用的表面活性剂均来自碳氢化合物来源，但最近人们一直在努力用可生物降解、无毒、生物合成的替代品来取代它们。之前的例子主要检查了天然存在的自组装蛋白质，例如丝和弹性蛋白样序列。在此，我们描述了一系列新的融合蛋白，这些融合蛋白已被开发出来，在酶裂解增溶蛋白标签后，可以自发地自组装成直径为 27 nm 的稳定胶束。这些蛋白质的序列基于人类本质上无序的蛋白质，该蛋白质已附加疏水性片段。研究发现胶束在较宽的 pH、离子强度和温度条件下形成，临界胶束浓度 (CMC) 值在低微摩尔范围内，比常用表面活性剂十二烷基硫酸钠 (SDS) 的 CMC 低 3 个数量级。所报道的胶束被发现可以溶解疏水性金属配合物和有机分子，表明它们对于催化和药物输送应用的潜在适用性。此外，这些蛋白质序列设计的固有灵活性使得能够为许多未来应用编码额外的功能。总体而言，这项工作代表了传统表面活性剂的一种新的生物分子替代品，传统表面活性剂基于不可再生且生物降解性差的碳氢化合物来源。
The self-assembly of micellar structures from diblock polymers that contain hydrophilic and hydrophobic domains has been of great interest for the encapsulation of drugs and other hydrophobic molecules. While most commercially used surfactants are derived from hydrocarbon sources, there have been recent efforts to replace these with biodegradable, nontoxic, biologically synthesized alternatives. Previous examples have primarily examined naturally occurring self-assembling proteins, such as silk and elastin-like sequences. Herein, we describe a new series of fusion proteins that have been developed to self-assemble spontaneously into stable micelles that are 27 nm in diameter after enzymatic cleavage of a solubilizing protein tag. The sequences of the proteins are based on a human intrinsically disordered protein, which has been appended with a hydrophobic segment. The micelles were found to form across a broad range of pH, ionic strength, and temperature conditions, with critical micelle concentration (CMC) values in the low micromolar range, 3 orders of magnitude lower than the CMC of commonly used surfactant sodium dodecyl sulfate (SDS). The reported micelles were found to solubilize hydrophobic metal complexes and organic molecules, suggesting their potential suitability for catalysis and drug delivery applications. Furthermore, the inherent flexibility in the design of these protein sequences enables the encoding of additional functionalities for many future applications. Overall, this work represents a new biomolecular alternative to traditional surfactants that are based on nonrenewable and poorly biodegradable hydrocarbon sources.