Fraccia Tommaso P, Jia Tony Z
Institut Pierre-Gilles de Gennes, Chimie Biologie Innovation, ESPCI Paris, CNRS, PSL Research University, 75005 Paris, France.
Earth-Life Science Institute, Tokyo Institute of Technology, 2-12-1-IE-1 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
ACS Nano. 2020 Nov 24;14(11):15071-15082. doi: 10.1021/acsnano.0c05083. Epub 2020 Sep 2.
Phase separation of nucleic acids and proteins is a ubiquitous phenomenon regulating subcellular compartment structure and function. While complex coacervation of flexible single-stranded nucleic acids is broadly investigated, coacervation of double-stranded DNA (dsDNA) is less studied because of its propensity to generate solid precipitates. Here, we reverse this perspective by showing that short dsDNA and poly-l-lysine coacervates can escape precipitation while displaying a surprisingly complex phase diagram, including the full set of liquid crystal (LC) mesophases observed to date in bulk dsDNA. Short dsDNA supramolecular aggregation and packing in the dense coacervate phase are the main parameters regulating the global LC-coacervate phase behavior. LC-coacervate structure was characterized upon variations in temperature and monovalent salt, DNA, and peptide concentrations, which allow continuous reversible transitions between all accessible phases. A deeper understanding of LC-coacervates can gain insights to decipher structures and phase transition mechanisms within biomolecular condensates, to design stimuli-responsive multiphase synthetic compartments with different degrees of order and to exploit self-assembly driven cooperative prebiotic evolution of nucleic acids and peptides.
核酸与蛋白质的相分离是一种普遍存在的现象，它调控着亚细胞区室的结构与功能。虽然对柔性单链核酸的复杂凝聚现象已有广泛研究，但双链DNA（dsDNA）的凝聚现象却较少被研究，因为它容易产生固体沉淀。在此，我们扭转了这一观点，表明短双链DNA与聚L-赖氨酸凝聚物能够避免沉淀，同时展现出令人惊讶的复杂相图，包括迄今为止在大量双链DNA中观察到的全套液晶（LC）中间相。短双链DNA在致密凝聚相中的超分子聚集和堆积是调节整体LC-凝聚相行为的主要参数。通过改变温度、单价盐、DNA和肽的浓度来表征LC-凝聚物结构，这使得在所有可及相之间能够进行连续可逆的转变。对LC-凝聚物的更深入理解有助于深入了解生物分子凝聚物中的结构和相变机制，设计具有不同有序程度的刺激响应多相合成区室，并利用自组装驱动的核酸和肽的协同益生元进化。
