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序列可编程核酸凝聚物

Sequence programmable nucleic acid coacervates.

作者信息

Majumder Sumit, Coupe Sebastian, Fakhri Nikta, Jain Ankur

机构信息

Whitehead Institute for Biomedical Research, Cambridge 02142, USA.

Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.

出版信息

bioRxiv. 2024 Jul 23:2024.07.22.604687. doi: 10.1101/2024.07.22.604687.

Abstract

Nature uses bottom-up self-assembly to build structures with remarkable complexity and functionality. Understanding how molecular-scale interactions translate to macroscopic properties remains a major challenge and requires systems that effectively bridge these two scales. Here, we generate DNA and RNA liquids with exquisite programmability in their material properties. Nucleic acids are negatively charged, and in the presence of polycations, they may condense to a liquid-like state. Within these liquids, DNA and RNA retain sequence-specific hybridization abilities. We show that intermolecular hybridization in the condensed phase cross-links molecules and slows down chain dynamics. This reduced chain mobility is mirrored in the macroscopic properties of the condensates. Molecular diffusivity and material viscosity scale with the intermolecular hybridization energy, enabling precise sequence-based modulation of condensate properties over orders of magnitude. Our work offers a robust platform to create self-assembling programmable fluids and may help advance our understanding of liquid-like compartments in cells.

摘要

自然界利用自下而上的自组装来构建具有显著复杂性和功能性的结构。理解分子尺度的相互作用如何转化为宏观性质仍然是一个重大挑战,并且需要能够有效连接这两个尺度的系统。在这里,我们生成了在材料性质方面具有精确可编程性的DNA和RNA液体。核酸带负电荷,在聚阳离子存在的情况下,它们可能会凝聚成类似液体的状态。在这些液体中,DNA和RNA保留了序列特异性杂交能力。我们表明,凝聚相中的分子间杂交会交联分子并减缓链动力学。这种降低的链流动性反映在凝聚物的宏观性质中。分子扩散率和材料粘度与分子间杂交能量成比例,从而能够在多个数量级上对凝聚物性质进行基于序列的精确调控。我们的工作提供了一个强大的平台来创建自组装可编程流体,并可能有助于推进我们对细胞中类似液体隔室的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8c8/11291106/e08c649a3957/nihpp-2024.07.22.604687v1-f0001.jpg

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