Dipartimento di Fisica e Chimica and Advanced Technologies Network Center (ATEN) , Università degli Studi di Palermo , Viale delle Scienze ed.18 , Palermo 90128 , Italy.
Department of Chemical Engineering and Biotechnology , University of Cambridge , Pembroke Street , Cambridge CB2 3RA , U.K.
J Phys Chem B. 2018 Mar 29;122(12):3101-3112. doi: 10.1021/acs.jpcb.8b01779. Epub 2018 Mar 15.
Protein self-assembly into amyloid fibrils or highly hierarchical superstructures is closely linked to neurodegenerative pathologies as Alzheimer's and Parkinson's diseases. Moreover, protein assemblies also emerged as building blocks for bioinspired nanostructured materials. In both the above mentioned fields, the main challenge is to control the growth and properties of the final protein structure. This relies on a more fundamental understanding of how interactions between proteins can determine structures and functions of biomolecular aggregates. Here, we identify a striking effect of the hydration of the single human insulin molecule and solvent properties in controlling hydrophobicity/hydrophilicity, structures, and morphologies of a superstructure named spherulite, observed in connection to Alzheimer's disease. Depending on the presence of ethanol, such structures can incorporate fluorescent molecules with different physicochemical features and span a range of mechanical properties and morphologies. A theoretical model providing a thorough comprehension of the experimental data is developed, highlighting a direct connection between the intimate physical protein-protein interactions, the growth, and the properties of the self-assembled superstructures. Our findings indicate structural variability as a general property for amyloid-like aggregates and not limited to fibrils. This knowledge is pivotal not only for developing effective strategies against pathological amyloids but also for providing a platform to design highly tunable biomaterials, alternative to elongated protein fibrils.
蛋白质自我组装成淀粉样纤维或高度分层的超结构，与神经退行性疾病（如阿尔茨海默病和帕金森病）密切相关。此外，蛋白质组装也成为仿生纳米结构材料的构建块。在上述两个领域，主要的挑战是控制最终蛋白质结构的生长和性质。这依赖于对蛋白质之间的相互作用如何决定生物分子聚集体的结构和功能有更基本的理解。在这里，我们发现单个人类胰岛素分子的水合作用和溶剂性质对控制疏水性/亲水性、结构和超结构形态（称为球晶）具有显著影响，这种超结构与阿尔茨海默病有关。根据乙醇的存在，这些结构可以包含具有不同物理化学特性的荧光分子，并具有广泛的机械性能和形态。提出了一个理论模型，该模型提供了对实验数据的透彻理解，强调了蛋白质-蛋白质相互作用的内在物理性质与自组装超结构的生长和性质之间的直接联系。我们的发现表明，结构可变性是淀粉样类聚集物的一般特性，而不仅仅局限于纤维。这一知识不仅对于开发针对病理性淀粉样蛋白的有效策略至关重要，而且为设计高度可调的生物材料提供了一个替代长蛋白纤维的平台。
