Amphiphilic Elastin-Like Block Co-Recombinamers Containing Leucine Zippers: Cooperative Interplay between Both Domains Results in Injectable and Stable Hydrogels
Amphiphilic Elastin-Like Block Co-Recombinamers Containing Leucine Zippers: Cooperative Interplay between Both Domains Results in Injectable and Stable Hydrogels
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DOI：
10.1021/acs.biomac.5b01103
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发表时间：
2015-10-01
影响因子：
6.2
通讯作者：
Carlos Rodriguez-Cabello, J.
中科院分区：
文献类型：
--
作者：
Fernandez-Colino, Alicia;Javier Arias, F.;Carlos Rodriguez-Cabello, J.
许多生物学过程是由可逆的结合事件调节的，这些大分子之间的相互作用代表了动态化学的核心。因此，任何试图更好地了解这种相互作用的尝试，这将为推断自然设计创造新的先进系统铺平道路，显然是令人感兴趣的。这项工作的重点是亮氨酸拉链弹性蛋白样重组体（ZELR）的发展，以阐明这些领域的行为时，共存沿着相同的分子和工程可逆的，可注射的和稳定的水凝胶。Z-部分选择二聚化的独特倾向，连同ELR的热敏行为，其已被构建为热敏性两亲性四嵌段，已被工程化为单个重组分子。在这种分子设计中，Z-部分不能形成网络，而ELR低于其Tt，因此，保证了系统的类液体状态。然而，这种情况随着温度升高超过Tt而迅速变化，其中形成稳定的水凝胶，如流变学测试所证明的。ELR分子（没有Z结构域）无法在Tt以上形成如此稳定的水凝胶，这清楚地表明这两个结构域（Z和EL）之间存在积极的协同效应，并且前者不涉及构象变化，正如圆二色性所证明的那样分析。AFM显示，Z-基序似乎诱导胶束的聚集，这支持了在宏观水平上与ELR相比时由ZELR显示的增强的稳定性。据我们所知，这是第一次报道这两个领域之间的这种相互作用。此外，所得水凝胶的细胞相容性为其在生物医学应用中的使用打开了大门。
Many biological processes are regulated by reversible binding events, with these interactions between macromolecules representing the core of dynamic chemistry. As such, any attempt to gain a better understanding of such interactions, which would pave the way to the extrapolation of natural designs to create new advanced systems, is clearly of interest. This work focuses on the development of a leucine zipper-elastin-like recombinamer (ZELR) in order to elucidate the behavior of such domains when coexisting along the same molecule and to engineer reversible, injectable and stable hydrogels. The unique propensity of the Z-moiety selected to dimerize, together with the thermosensitive behavior of the ELR, which has been constructed as a thermosensitive amphiphilic tetrablock, has been engineered into a single recombinant molecule. In this molecular design, the Z-moieties are unable to form a network, while the ELR is below its Tt, thus, guaranteeing the liquid-like state of the system. However, this situation changes rapidly as the temperature increases above Tt, where a stable hydrogel is formed, as demostrated by rheological tests. The inability of the ELR molecule (without Z-domains) to form such a stable hydrogel above Tt clearly points to a positive cooperative effect between these two domains (Z and EL), and no conformational changes in the former are involved, as demonstrated by circular dichroism analysis. AFM shows that Z-motifs seem to induce the aggregation of micelles, which supports the enhanced stability displayed by ZELRs when compared to ELR at the macroscale level. To the best of our knowledge, this is the first time that such an interplay between these two domains has been reported. Furthermore, the cytocompatibility of the resulting hydrogels opens the door to their use in biomedical applications.