Department of Chemistry , University of California , Berkeley , California 94720 , United States.
Department of Bioengineering , University of California , Berkeley , California 94720 , United States.
J Am Chem Soc. 2019 Mar 13;141(10):4291-4299. doi: 10.1021/jacs.8b10688. Epub 2019 Feb 26.
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.
两亲嵌段聚合物自组装形成胶束结构，可用于包封药物和其他疏水分子。虽然大多数市售表面活性剂来源于碳氢化合物，但近来人们一直致力于用可生物降解、无毒、生物合成的替代品替代这些表面活性剂。以前的例子主要研究了天然存在的自组装蛋白质，如丝蛋白和弹性蛋白样序列。本文描述了一系列新的融合蛋白，它们经过酶切可溶性蛋白标签后，能够自发组装成直径为 27nm 的稳定胶束。这些蛋白质的序列基于一种人类天然无序蛋白，该蛋白被添加了一个疏水片段。这些胶束在很宽的 pH 值、离子强度和温度范围内形成，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 值低 3 个数量级。研究发现，所报道的胶束能够溶解疏水性金属配合物和有机分子，表明它们可能适用于催化和药物输送应用。此外，这些蛋白质序列的设计具有固有灵活性，可用于许多未来应用的额外功能编码。总的来说，这项工作代表了一种新的生物分子替代传统表面活性剂的方法，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。
