Life-Like Materials and Systems, Department of Chemistry, University of Mainz, Mainz 55128, Germany.
Max Planck Institute for Polymer Research, Mainz 55128, Germany.
Biomacromolecules. 2024 Sep 9;25(9):5468-5488. doi: 10.1021/acs.biomac.4c00814. Epub 2024 Aug 23.
Biomolecular condensates are dynamic liquid droplets through intracellular liquid-liquid phase separation that function as membraneless organelles, which are highly involved in various complex cellular processes and functions. Artificial analogs formed via similar pathways that can be integrated with biological complexity and advanced functions have received tremendous research interest in the field of synthetic biology. The coacervate droplet-based compartments can partition and concentrate a wide range of solutes, which are regarded as attractive candidates for mimicking phase-separation behaviors and biophysical features of biomolecular condensates. The use of peptide-based materials as phase-separating components has advantages such as the diversity of amino acid residues and customized sequence design, which allows for programming their phase-separation behaviors and the physicochemical properties of the resulting compartments. In this Perspective, we highlight the recent advancements in the design and construction of biomimicry condensates from synthetic peptides relevant to intracellular phase-separating protein, with specific reference to their molecular design, self-assembly via phase separation, and biorelated applications, to envisage the use of peptide-based droplets as emerging biomedical delivery vehicles.
生物分子凝聚物是通过细胞内液-液相分离形成的动态液相微滴,作为无膜细胞器发挥作用,它们高度参与各种复杂的细胞过程和功能。通过类似途径形成的人工类似物可以与生物复杂性和先进功能相结合,在合成生物学领域引起了极大的研究兴趣。凝聚相液滴基隔室可以分隔和浓缩广泛的溶质,这些溶质被认为是模拟生物分子凝聚物的相分离行为和生物物理特性的有吸引力的候选物。使用基于肽的材料作为相分离成分具有许多优势,例如氨基酸残基的多样性和定制序列设计,这允许对其相分离行为和所得隔室的物理化学性质进行编程。在本观点中,我们强调了从与细胞内相分离蛋白相关的合成肽设计和构建仿生凝聚物的最新进展,特别参考了它们的分子设计、通过相分离的自组装以及生物相关应用,以设想将基于肽的液滴用作新兴的生物医学递药载体。