基于肽的自组装水凝胶已经成为用于三维(3D)体外疾病建模的非常有吸引力的支架,因为它们提供了一种创建可类似于各种微环境的细胞外基质(ECM)的可调基质的方法。阿尔茨海默病(AD)是一种异常复杂的神经退行性疾病;然而,由于从二维(2D)到3D体外建模的过渡,我们的理解已经进步。尽管如此,关于淀粉样蛋白结构的作用,和先前开发的模型发现,在创建涉及ECM和淀粉样蛋白聚集体的适当模型方面存在长期困难。在这份报告中,我们提出了一种多组分自组装的基于肽的水凝胶支架来模拟含有淀粉样蛋白β(β)的微环境。淀粉样蛋白-β模拟水凝胶(Col-HAMA-FF)的表征表明,由于苯丙氨酸的自组装特性(Phe,F)通过残基的π-π堆叠,从而模拟淀粉样β蛋白纳米结构。与天然模拟基质(Col-HAMA)相比,我们研究了淀粉样蛋白-β模拟微环境对健康神经元祖细胞(NPC)的影响。我们的结果表明,与天然脑基质相比,当NPC在淀粉样蛋白样基质中培养时,神经炎症和凋亡标志物的水平更高。这里,我们提供了有关淀粉样蛋白结构对NPC表型和行为的影响的见解。这项基础性工作,在发展到更复杂的斑块模型之前,为AD机制和药物测试的未来研究提供了有希望的支架。重要声明:在这项研究中,我们设计了两种多组分水凝胶:一种是模拟大脑的天然细胞外基质(ECM),另一种是使用自组装肽水凝胶类似淀粉样微环境。自组装肽模拟在淀粉样β蛋白聚集体中看到的β-淀粉样原纤维。我们报告了模拟淀粉样蛋白的ECM支架中神经元祖细胞的培养,以研究与炎症和DNA损伤相关的标记表达的影响。这项基础性工作,在发展到更复杂的斑块模型之前,为未来AD机制和药物测试的研究提供了一个有前途的支架。这适合您的读者,因为它适合用于建模和理解生物相互作用的假设驱动的生物材料设计的范围。
Self-assembling peptide-based hydrogels have become a highly attractive scaffold for three-dimensional (3D) in vitro disease modeling as they provide a way to create tunable matrices that can resemble the extracellular matrix (ECM) of various microenvironments. Alzheimer\'s disease (AD) is an exceptionally complex neurodegenerative condition; however, our understanding has advanced due to the transition from two-dimensional (2D) to 3D in vitro modeling. Nonetheless, there is a current gap in knowledge regarding the role of amyloid structures, and previously developed models found long-term difficulty in creating an appropriate model involving the ECM and amyloid aggregates. In this report, we propose a multi-component self-assembling peptide-based hydrogel scaffold to mimic the amyloid-beta (β) containing microenvironment. Characterization of the amyloid-β-mimicking hydrogel (Col-HAMA-FF) reveals the formation of β-sheet structures as a result of the self-assembling properties of phenylalanine (Phe, F) through π-π stacking of the residues, thus mimicking the amyloid-β protein nanostructures. We investigated the effect of the amyloid-β-mimicking microenvironment on healthy neuronal progenitor cells (NPCs) compared to a natural-mimicking matrix (Col-HAMA). Our results demonstrated higher levels of neuroinflammation and apoptosis markers when NPCs were cultured in the amyloid-like matrix compared to a natural brain matrix. Here, we provided insights into the impact of amyloid-like structures on NPC phenotypes and behaviors. This foundational work, before progressing to more complex plaque models, provides a promising scaffold for future investigations on AD mechanisms and drug testing. STATEMENT OF SIGNIFICANCE: In this study, we engineered two multi-component hydrogels: one to mimic the natural extracellular matrix (ECM) of the brain and one to resemble an amyloid-like microenvironment using a self-assembling peptide hydrogel. The self-assembling peptide mimics β-amyloid fibrils seen in amyloid-β protein aggregates. We report on the culture of neuronal progenitor cells within the amyloid-mimicking ECM scaffold to study the impact through marker expressions related to inflammation and DNA damage. This foundational work, before progressing to more complex plaque models, offers a promising scaffold for future investigations on AD mechanisms and drug testing.