Soliman Mohamed A N, Khedr Abdulwahhab, Sahota Tarsem, Armitage Rachel, Allan Raymond, Laird Katie, Allcock Natalie, Ghuloum Fatmah I, Amer Mahetab H, Alazragi Reem, Edwards-Gayle Charlotte J C, Wychowaniec Jacek K, Vargiu Attilio V, Elsawy Mohamed A
Leicester Institute for Pharmaceutical Innovation, Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Small. 2025 Feb;21(6):e2408213. doi: 10.1002/smll.202408213. Epub 2025 Jan 9.
Guiding molecular assembly of peptides into rationally engineered nanostructures remains a major hurdle against the development of functional peptide-based nanomaterials. Various non-covalent interactions come into play to drive the formation and stabilization of these assemblies, of which electrostatic interactions are key. Here, the atomistic mechanisms by which electrostatic interactions contribute toward controlling self-assembly and lateral association of ultrashort β-sheet forming peptides are deciphered. Our results show that this is governed by charge distribution and ionic complementarity, both affecting the interaction patterns between charged residues: terminal, core, and/or terminal-to-core attraction/repulsion. Controlling electrostatic interactions enabled fine-tuning nanofiber morphology for the 16 examined peptides, resulting into versatile nanostructures ranging from extended thin fibrils and thick bundles to twisted helical "braids" and short pseudocrystalline nanosheets. This in turn affected the physical appearance and viscoelasticity of the formed materials, varying from turbid colloidal dispersions and viscous solutions to soft and stiff self-supportive hydrogels, as revealed from oscillatory rheology. Atomistic mechanisms of electrostatic interaction patterns were confirmed by molecular dynamic simulations, validating molecular and nanoscopic characterization of the developed materials. In essence, detailed mechanisms of electrostatic interactions emphasizing the impact of charge distribution and ionic complementarity on self-assembly, nanostructure formation, and hydrogelation are reported.
引导肽分子组装成合理设计的纳米结构仍然是功能性肽基纳米材料发展的主要障碍。各种非共价相互作用在驱动这些组装体的形成和稳定中发挥作用，其中静电相互作用是关键。在此，我们破译了静电相互作用有助于控制超短β-折叠形成肽的自组装和横向缔合的原子机制。我们的结果表明，这由电荷分布和离子互补性决定，二者均影响带电残基之间的相互作用模式：末端、核心和/或末端到核心的吸引/排斥。通过控制静电相互作用，能够对16种受试肽的纳米纤维形态进行微调，从而产生从细长纤维、粗束到扭曲螺旋“辫状物”和短假晶纳米片等多种纳米结构。如振荡流变学所示，这反过来又影响了所形成材料的物理外观和粘弹性，从浑浊的胶体分散体和粘性溶液到柔软和坚硬的自支撑水凝胶不等。通过分子动力学模拟证实了静电相互作用模式的原子机制，验证了所开发材料的分子和纳米尺度表征。本质上，本文报道了强调电荷分布和离子互补性对自组装、纳米结构形成和水凝胶化影响的静电相互作用详细机制。
