Switchable Self-Assembly of Elastin- and Resilin-Based Block Copolypeptides with Converse Phase Transition Behaviors
Switchable Self-Assembly of Elastin- and Resilin-Based Block Copolypeptides with Converse Phase Transition Behaviors
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DOI：
10.1021/acsami.1c00676
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发表时间：
2021-05-18
影响因子：
9.5
通讯作者：
Lim, Dong Woo
中科院分区：
文献类型：
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作者：
Basheer, Aamna;Shahid, Shahzaib;Lim, Dong Woo
热响应性多肽自组装成独特的纳米结构为智能生物纳米材料提供了有趣的属性，包括动态物理尺寸、生物兼容性和生物降解性。随着具有较低临界溶解温度(LCST)的弹性蛋白多肽(EBP)融合蛋白作为药物载体的研究，基于Resilin的多肽(RBP)具有较高临界溶解温度(UCST)的EBP嵌段共聚多肽引起了人们的极大兴趣。在这项研究中，我们报道了在生理条件下，基于EBP和RBP的双嵌段共聚肽在热触发下动态自组装成具有可逆性的开关纳米结构。通过递归定向连接的方法合成了不同区段长度比的EBP-RBP双区块的分子DNA克隆，并进行了高效表达，然后通过逆转换循环进行非层析纯化。由EBP与LcST和RBP与UCST组成的基因工程双嵌段共聚肽表现出相反的相变行为，既有明显的LCST，又有明显的UCST(LCST<；UCST)。随着温度的升高，这些EBP-RBP嵌段有三个相：(1)在LCST和UCST下方形成自组装胶束或囊泡；(2)在LCST上方和UCST下方形成完整的聚集体；(3)在LCST和UCST上方形成反胶束。总之，这些由刺激触发的、动态的基于蛋白质的纳米结构有望用于先进的药物输送系统、再生医学和生物医学纳米技术。
Self-assembly of thermally responsive polypeptides into unique nanostructures offers intriguing attributes including dynamic physical dimensions, biocompatibility, and biodegradability for the smart bio-nanomaterials. As elastin-based polypeptide (EBP) fusion proteins with lower critical solution temperature (LCST) are studied as drug delivery systems, EBP block copolypeptides with the resilin-based polypeptide (RBP) displaying an upper critical solution temperature (UCST) have been of great interest. In this study, we report thermally triggered, dynamic self-assembly of EBP- and RBP-based diblock copolypeptides into switched nanostructures with reversibility under physiological conditions. Molecular DNA clones encoding for the EBP-RBP diblocks at different block length ratios were biosynthesized via recursive directional ligation and overexpressed, followed by nonchromatographic purification by inverse transition cycling. Genetically engineered diblock copolypeptides composed of the EBP with an LCST and the RBP with a UCST showed converse phase transition behaviors with both a distinct LCST and a distinct UCST (LCST < UCST). As temperature increased, three phases of these EBP-RBP diblocks were observed: (1) self-assembled micelles or vesicles below both LCST and UCST, (2) whole aggregates above LCST and below UCST, and (3) reversed micelles above both LCST and UCST. In conclusion, these stimuli-triggered, dynamic protein-based nanostructures are promising for advanced drug delivery systems, regenerative medicine, and biomedical nanotechnology.