Rajagopal Karthikan, Ozbas Bulent, Pochan Darrin J, Schneider Joel P
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716, USA.
Eur Biophys J. 2006 Jan;35(2):162-9. doi: 10.1007/s00249-005-0017-7. Epub 2005 Nov 8.
A class of peptides has been designed whose ability to self-assemble into hydrogel is dependent on their conformationally folded state. Under unfolding conditions aqueous peptide solutions are freely flowing having the viscosity of water. When folding is triggered by external stimuli, peptides adopt a beta-hairpin conformation that self-assembles into a highly crosslinked network of fibrils affording mechanically rigid hydrogels. MAX 1, a 20 residue, amphiphilic hairpin self-assembles via a mechanism which entails both lateral and facial self-assembly events to form a network of fibrils whose local structure consists of a bilayer of hairpins hydrogen bonded in the direction of fibril growth. Lateral self-assembly along the long axis of the fibril is mainly facilitated by intermolecular hydrogen bonding between the strands of distinct hairpins and the formation of hydrophobic contacts between residue side chains of laterally associating hairpins. Facial assembly is driven by the hydrophobic collapse of the valine-rich faces of the amphiphilic hairpins affording a bilayer laminate. The importance of forming lateral hydrophobic contacts during hairpin self-assembly and the relative contribution these interactions have towards nano-scale morphology and material rigidity is probed via the study of: MAX1, a hairpin designed to exploit lateral hydrophobic interactions; MAX 4, a peptide with reduced ability to form these interactions; and MAX5, a control peptide. CD spectroscopy and rheological experiments suggest that the formation of lateral hydrophobic interactions aids the kinetics of assembly and contributes to the mechanical rigidity of the hydrogel. Transmission electron microscopy (TEM) shows that these interactions play an essential role in the self-assembly process leading to distinct nano-scale morphologies.
已设计出一类肽，其自组装成水凝胶的能力取决于它们的构象折叠状态。在未折叠条件下，肽水溶液自由流动，具有水的粘度。当由外部刺激触发折叠时，肽会采用β-发夹构象，该构象自组装成高度交联的纤维网络，从而形成机械刚性水凝胶。MAX 1是一种由20个残基组成的两亲性发夹，通过一种既包含横向又包含面内自组装事件的机制进行自组装，形成一个纤维网络，其局部结构由沿纤维生长方向氢键结合的发夹双层组成。沿纤维长轴的横向自组装主要由不同发夹链之间的分子间氢键以及横向缔合发夹的残基侧链之间形成的疏水接触促进。面内组装由两亲性发夹富含缬氨酸面的疏水塌缩驱动，形成双层叠片。通过对以下肽的研究来探究在发夹自组装过程中形成横向疏水接触的重要性以及这些相互作用对纳米级形态和材料刚性的相对贡献：MAX1，一种旨在利用横向疏水相互作用设计的发夹；MAX 4，一种形成这些相互作用能力降低的肽；以及MAX5，一种对照肽。圆二色光谱（CD）和流变学实验表明，横向疏水相互作用的形成有助于组装动力学，并有助于水凝胶的机械刚性。透射电子显微镜（TEM）显示，这些相互作用在导致不同纳米级形态的自组装过程中起着至关重要的作用。
