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多凝聚态作为一种优化细胞信号输出的功能策略。

Multi-condensate state as a functional strategy to optimize the cell signaling output.

机构信息

Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA.

出版信息

Nat Commun. 2024 Jul 25;15(1):6268. doi: 10.1038/s41467-024-50489-5.

Abstract

The existence of multiple biomolecular condensates inside living cells is a peculiar phenomenon not compatible with the predictions of equilibrium statistical mechanics. In this work, we address the problem of multiple condensates state (MCS) from a functional perspective. We combine Langevin dynamics, reaction-diffusion simulation, and dynamical systems theory to demonstrate that MCS can indeed be a function optimization strategy. Using Arp2/3 mediated actin nucleation pathway as an example, we show that actin polymerization is maximum at an optimal number of condensates. For a fixed amount of Arp2/3, MCS produces a greater response compared to its single condensate counterpart. Our analysis reveals the functional significance of the condensate size distribution which can be mapped to the recent experimental findings. Given the spatial heterogeneity within condensates and non-linear nature of intracellular networks, we envision MCS to be a generic functional solution, so that structures of network motifs may have evolved to accommodate such configurations.

摘要

活细胞内存在多种生物分子凝聚物是一种特殊现象,与平衡统计力学的预测不兼容。在这项工作中,我们从功能的角度来解决多凝聚物状态(MCS)的问题。我们结合了朗之万动力学、反应扩散模拟和动力系统理论,证明了 MCS 确实可以作为一种函数优化策略。我们以 Arp2/3 介导的肌动蛋白成核途径为例,表明肌动蛋白聚合在最佳凝聚物数量下达到最大值。对于固定量的 Arp2/3,MCS 产生的响应比其单个凝聚物对应物更大。我们的分析揭示了凝聚物大小分布的功能意义,这可以映射到最近的实验发现。鉴于凝聚物内的空间异质性和细胞内网络的非线性性质,我们设想 MCS 是一种通用的功能解决方案,因此网络基元的结构可能已经进化到适应这种配置。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b63/11272944/2a177d6a11d9/41467_2024_50489_Fig1_HTML.jpg

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