Rajagopal Karthikan, Lamm Matthew S, Haines-Butterick Lisa A, Pochan Darrin J, Schneider Joel P
Department of Chemistry and Biochemistry, University of Delaware, Newark Delaware 19716, USA.
Biomacromolecules. 2009 Sep 14;10(9):2619-25. doi: 10.1021/bm900544e.
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).
本文提出了一种设计策略，用于以pH依赖的方式控制两亲性β-发夹肽的热触发折叠、自组装及随后的水凝胶化。对自组装肽MAX1的赖氨酸残基进行点突变，以改变肽的净电荷。相应地，肽的静电性质直接影响允许热触发水凝胶化的溶液pH值。圆二色光谱和振荡流变学表明，在给定温度下，净正电荷较低的肽能够在较低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，还取决于肽序列内取代的精确位置。透射电子显微镜显示，这些肽自组装成由形态明确的非层状原纤维组成的水凝胶。透射电子显微镜还表明，在发夹亲水面上进行这些序列改变不会影响原纤维形态。流变学表明，这些肽水凝胶的最终机械刚性取决于折叠和自组装的速率。折叠和组装更快的肽能形成更刚性的凝胶。最终，这种设计策略产生了一种肽MAX1(K15E)，它能够在生理缓冲条件（pH 7.4、150 mM NaCl、37℃）下发生热触发水凝胶化。
