Protein Engineered Triblock Polymers Composed of Two SADs: Enhanced Mechanical Properties and Binding Abilities,Biomacromolecules

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Protein Engineered Triblock Polymers Composed of Two SADs: Enhanced Mechanical Properties and Binding Abilities
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-03-15 00:00:00 , DOI: 10.1021/acs.biomac.7b01259
Andrew J. Olsen ₁ , Priya Katyal ₁ , Jennifer S. Haghpanah ₁ , Matthew B. Kubilius ₂ , Ruipeng Li ₃ , Nicole L. Schnabel ₁ , Sean C. O’Neill ₂ , Yao Wang ₁ , Min Dai ₁ , Navjot Singh ₁ , Raymond S. Tu ₂ , Jin Kim Montclare _{1,

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Affiliation

Recombinant methods have been used to engineer artificial protein triblock polymers composed of two different self-assembling domains (SADs) bearing one elastin (E) flanked by two cartilage oligomeric matrix protein coiled-coil (C) domains to generate CEC. To understand how the two C domains improve small molecule recognition and the mechanical integrity of CEC, we have constructed C_L44AEC_L44A, which bears an impaired C_L44A domain that is unstructured as a negative control. The CEC triblock polymer demonstrates increased small molecule binding and ideal elastic behavior for hydrogel formation. The negative control C_L44AEC_L44A does not exhibit binding to small molecule and is inelastic at lower temperatures, affirming the favorable role of C domain and its helical conformation. While both CEC and C_L44AEC_L44A assemble into micelles, CEC is more densely packed with C domains on the surface enabling the development of networks leading to hydrogel formation. Such protein engineered triblock copolymers capable of forming robust hydrogels hold tremendous promise for biomedical applications in drug delivery and tissue engineering.

中文翻译：

由两种SAD组成的蛋白质工程三嵌段聚合物：增强的机械性能和结合能力

重组方法已用于工程化人工蛋白质三嵌段聚合物，该聚合物由两个不同的自组装域（SAD）组成，两个自组装域（SAD）带有一个弹性蛋白（E），两侧是两个软骨低聚基质蛋白卷曲螺旋（C）域，以生成CEC。为了了解这两个C结构域如何改善小分子识别和CEC的机械完整性，我们构建了C _L44A EC _L44A，其带有受损的C _L44A结构域，该结构域未_构建为阴性对照。CEC三嵌段聚合物显示出增加的小分子结合力和理想的弹性行为，可形成水凝胶。阴性对照C _L44A EC _L44A不显示与小分子的结合并且在较低温度下是无弹性的，这证实了C结构域及其螺旋构象的有利作用。虽然CEC和C _L44A EC _L44A都组装成胶束，但CEC的表面上C域更密集地堆积，从而能够形成导致水凝胶形成的网络。这种能够形成坚固水凝胶的蛋白质工程化的三嵌段共聚物，对于药物输送和组织工程中的生物医学应用具有广阔的前景。

更新日期：2018-03-15

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