Tuning the pH Responsiveness of β-Hairpin Peptide Folding, Self-Assembly, and Hydrogel Material Formation
Tuning the pH Responsiveness of β-Hairpin Peptide Folding, Self-Assembly, and Hydrogel Material Formation
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DOI：
10.1021/bm900544e
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发表时间：
2009-09-01
影响因子：
6.2
通讯作者：
Schneider, Joel P.
中科院分区：
文献类型：
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作者：
Rajagopal, Karthikan;Lamm, Matthew S.;Schneider, Joel P.
设计策略，以控制热触发折叠，自组装，和随后的水凝胶化的两亲性β-发夹肽在pH值依赖性的方式。对自组装肽MAX 1的赖氨酸残基进行点取代以改变肽的净电荷。反过来，肽的静电性质直接影响允许热触发水凝胶化的溶液pH。CD光谱和振荡流变学显示，较低净正电荷的肽能够在给定温度下在较低pH值下折叠并组装成水凝胶材料。pH敏感的折叠和组装行为不仅取决于肽的净电荷，而且还取决于肽序列内取代的确切位置。TEM显示，这些肽自组装成水凝胶是由明确的原纤维与非层压形态。TEM还表明，原纤维形态不受这些序列的变化上的发夹的亲水面的影响。流变学表明，这些肽水凝胶的最终机械刚度取决于折叠和自组装的速率。折叠和组装更快的肽提供更刚性的凝胶。最终，这种设计策略产生了能够在生理缓冲液条件（pH 7.4，150 NaCl，37 ℃）下经历热触发水凝胶化的肽MAX 1（K15 E）。
A design strategy to control the thermally triggered folding, self-assembly, and subsequent hydrogelation of amphiphilic beta-hairpin peptides in a pH-dependent manner is presented. Point substitutions of the lysine residues of the self-assembling peptide MAX1 were made to alter the net charge of the peptide. In turn, the electrostatic nature of the peptide directly influences the solution pH at which thermally triggered hydrogelation is permitted. CD spectroscopy and oscillatory rheology show that peptides of lower net positive charge are capable of folding and assembling into hydrogel material at lower values of pH at a given temperature. The pH sensitive folding and assembling behavior is not only dependent on the net peptide charge, but also on the exact position of substitution within the peptide sequence. TEM shows that these peptides self-assemble into hydrogels that are composed of well-defined fibrils with nonlaminated morphologies. TEM also indicates that fibril morphology is not influenced by making these sequence changes on the hydrophilic face of the hairpins. Rheology shows that the ultimate mechanical rigidity of these peptide hydrogels is dependent on the rate of folding and self-assembly. Peptides that fold and assemble faster afford more rigid gels. Ultimately, this design strategy yielded a peptide MAX1(K15E) that is capable of undergoing thermally triggered hydrogelation at physiological buffer conditions (pH 7.4, 150 NaCl, 37 degrees C).