A modular approach to the design of protein-based smart gels

A modular approach to the design of protein-based smart gels
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DOI:
10.1002/bip.22033
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发表时间:
2012-07-01
期刊:
影响因子:
2.9
通讯作者:
Regan, Lynne
Regan, Lynne
中科院分区:
生物学4区
文献类型:
--
作者:
Grove, Tijana Z.;Forster, Jason;Regan, Lynne

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重复蛋白质的模块化性质使其成为设计具有预定特性的智能材料的多功能平台。在这里,我们提出了一种将具有特定稳定性和功能的蛋白质模块组合到阵列中以组装刺激响应凝胶的一般策略。我们设计了四肽重复 (TPR) 阵列,其中包含指定网络交联强度和可逆性的肽结合模块以及指定交联几何形状和阵列整体稳定性的间隔模块。通过将此类阵列与多价肽配体组合,形成自支撑刺激响应凝胶。利用微观流变学,我们将凝胶动力学表征为成分浓度和化学计量的函数。我们还表明,这种凝胶可以有效地封装和释放小分子。此外,单独的 TPR 凝胶与细胞生长完全相容,而负载抗癌化合物的凝胶会释放该化合物,导致细胞死亡。因此,我们已经证明,这种新型可调节生物材料作为组织工程和药物输送平台的进一步开发已经成熟。 (c) 2012 Wiley periodicals, Inc. 生物聚合物 97:508519,2012。
The modular nature of repeat proteins makes them a versatile platform for the design of smart materials with predetermined properties. Here, we present a general strategy for combining protein modules with specified stability and function into arrays for the assembly of stimuli-responsive gels. We have designed tetratricopeptide repeat (TPR) arrays which contain peptide-binding modules that specify the strength and reversibility of network crosslinking in combination with spacer modules that specify crosslinking geometry and overall stability of the array. By combining such arrays with multivalent peptide ligands, self-supporting stimuli-responsive gels are formed. Using microrheology, we characterized the kinetics of gelation as a function of concentration and stoichiometry of the components. We also show that such gels are effective in encapsulating and releasing small molecules. Moreover, TPR gels alone are fully compatible with cell growth, whereas gels loaded with an anticancer compound release the compound, resulting in cell death. Thus, we have demonstrated that this new class of tunable biomaterials is ripe for further development as tissue engineering and drug delivery platform. (c) 2012 Wiley Periodicals, Inc. Biopolymers 97:508519, 2012.