Abstract:
Biological components (protein, DNA, lipid rafts, etc.) self-sort to form higher-order structures with elegant modulation by endogenous stimuli for maintaining cellular functions in living cells. However, the challenge of producing self-sorted higher-order assemblies of peptides in living systems (cells and tissues) spatiotemporally has yet to be achieved. This work reports the using of a biocompatible strategy to construct self-sorted assemblies of peptides in living cells and tumor-bearing mice. The results show that the designed peptides self-sort to form distinct nanostructures in living cancer cells using an endogenous trigger, as evidenced by confocal laser scanning microscopy and Bio-EM. Wound-healing experiments indicate that the in situ generation of self-sorted nanostructures exhibits a synergistic effect that significantly decreases the migration of cancer cells. In vivo experiments demonstrate that the designed peptides could self-sort in tumor-bearing mice and improve the tumor penetrating ability of the impenetrable component in tumor tissue. We can further program the formation of self-sorted materials through orthogonal triggers by introducing an exogenous trigger (light) and an endogenous trigger independently. Thus, this work provides a strategy to control multiple self-assembling processes in the context of the living system and provides a general strategy to construct self-sorted structures for the emergent properties of materials science.
摘要:
生物成分(蛋白质,DNA,脂筏,等。)自我排序以形成具有内源性刺激的优雅调节的高阶结构,以维持活细胞中的细胞功能。然而,在活系统(细胞和组织)中时空产生肽的自分选高阶组装体的挑战尚未实现。这项工作报告了使用生物相容性策略在活细胞和荷瘤小鼠中构建肽的自分选组装体。结果表明,设计的肽可以使用内源性触发剂在活癌细胞中自我分类以形成不同的纳米结构,共聚焦激光扫描显微镜和Bio-EM证明了这一点。伤口愈合实验表明,自分选纳米结构的原位生成表现出显著降低癌细胞迁移的协同效应。体内实验表明,设计的肽可以在荷瘤小鼠体内自我分类,并提高肿瘤组织中不可渗透成分的肿瘤穿透能力。我们可以通过独立地引入外源触发(光)和内源触发,通过正交触发进一步编程自分选材料的形成。因此,这项工作提供了一种在生命系统背景下控制多个自组装过程的策略,并提供了一种为材料科学的新兴特性构建自分类结构的一般策略。