Department of Biotechnology, National Institute of Technology Durgapur, Durgapur 713209, India.
The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
J Mater Chem B. 2024 Aug 28;12(34):8444-8453. doi: 10.1039/d4tb00948g.
Multicomponent biomolecular self-assembly is fundamental for accomplishing complex functionalities of biosystems. Self-assembling peptides, amino acids, and their conjugates serve as a versatile platform for developing biomaterials. However, the co-assembly of multiple building blocks showing synergistic interplay between individual components and producing biomaterials with emergent functional attributes is much less explored. In this study, we have formulated minimalistic co-assembled hydrogels composed of Fmoc-phenylalanine and Fmoc-lysine. The co-assembled systems display broad-spectrum antimicrobial potency, a feature absent in individual building blocks. A comprehensive biophysical analysis demonstrates the physicochemical features of the hydrogels eliciting the antibacterial response. MD simulation further reveals a unique fibrillar architecture with Fmoc-phenylalanine forming the fibril core surrounded by positively charged Fmoc-lysine surface residues, thereby enhancing the interaction with negatively charged bacterial membranes, causing membrane disruption and cell death. Thus, this study provides molecular-level insight into the emergent properties of a multicomponent system, affording an excellent paradigm for developing novel biomaterials.
多组分生物分子自组装是实现生物系统复杂功能的基础。自组装肽、氨基酸及其缀合物为开发生物材料提供了一个通用平台。然而，对于多个构建块的共组装，这些构建块表现出单个组件之间的协同相互作用，并产生具有新兴功能属性的生物材料，这方面的研究还很少。在这项研究中，我们设计了由 Fmoc-苯丙氨酸和 Fmoc-赖氨酸组成的极简共组装水凝胶。共组装系统显示出广谱抗菌效力，这是单个构建块所没有的特性。全面的生物物理分析证明了水凝胶的物理化学特性引发了抗菌反应。分子动力学模拟进一步揭示了一种独特的纤维状结构，其中 Fmoc-苯丙氨酸形成纤维核心，周围是带正电荷的 Fmoc-赖氨酸表面残基，从而增强了与带负电荷的细菌膜的相互作用，导致膜破裂和细胞死亡。因此，这项研究提供了对多组分系统涌现特性的分子水平洞察，为开发新型生物材料提供了一个极好的范例。
