Quantitative model of the phase behavior of recombinant pH-responsive elastin-like polypeptides.

Quantitative model of the phase behavior of recombinant pH-responsive elastin-like polypeptides.
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DOI:
10.1021/bm100571j
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发表时间:
2010-11-08
期刊:
影响因子:
6.2
通讯作者:
Chilkoti, Ashutosh
Chilkoti, Ashutosh
中科院分区:
化学2区
文献类型:
--
作者:
MacKay, J. Andrew;Callahan, Daniel J.;FitzGerald, Kelly N.;Chilkoti, Ashutosh

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需要定量模型来设计具有环境响应特性的生物材料。考虑到这一目标,我们开发了一个模型,描述了一类刺激响应性弹性蛋白样多肽(ELP)的pH依赖性相行为进行可逆的相分离,以响应其溶液环境。在等温条件下,带电的ELP在其电荷被中和时可以经历相分离。这种行为的优化一直具有挑战性,因为它们相分离时的pH(pHt)取决于它们的组成、分子量、浓度和温度。为了解决这个问题,我们开发了一个定量模型来描述带电ELP的相行为,该模型使用Henderson-Hasselbalch关系来描述侧链电离对ELP相变温度的影响。用含有酸性(Glu)或碱性(His)残基的pH响应ELP验证该模型。两种ELP的相分离在一定pH范围内均符合该模型。这些结果对pH响应性弹性蛋白样多肽的应用具有重要意义,因为它们为合理设计pH响应性多肽提供了定量模型,其转变可以在特定pH下触发。
Quantitative models are required to engineer biomaterials with environmentally responsive properties. With this goal in mind, we developed a model that describes the pH dependent phase behavior of a class of stimulus responsive elastin-like polypeptides (ELPs) that undergo reversible phase separation in response to their solution environment. Under isothermal conditions, charged ELPs can undergo phase separation when their charge is neutralized. Optimization of this behavior has been challenging because the pH at which they phase separate, pHt, depends on their composition, molecular weight, concentration, and temperature. To address this problem, we developed a quantitative model to describe the phase behavior of charged ELPs that uses the Henderson-Hasselbalch relationship to describe the effect of side-chain ionization on the phase transition temperature of an ELP. The model was validated with pH-responsive ELPs that contained either acidic (Glu) or basic (His) residues. The phase separation of both ELPs fit this model across a range of pH. These results have important implications for applications of pH-responsive elastin-like polypeptides, because they provide a quantitative model for the rational design of pH responsive polypeptides whose transition can be triggered at a specified pH.
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