Synthetic Membraneless Droplets for Synaptic-Like Clustering of Lipid Vesicles

Qingchuan Li; Qingchun Song; Wei Guo; Yang Cao; Xinyu Cui; Dairong Chen; Ho Cheung Shum

doi:10.1002/anie.202313096

Synthetic Membraneless Droplets for Synaptic-Like Clustering of Lipid Vesicles

Qingchuan Li^*, Qingchun Song, Wei Guo, Yang Cao, Xinyu Cui, Dairong Chen^*, Ho Cheung Shum^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

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Abstract

In eukaryotic cells, the membraneless organelles (MLOs) formed via liquid-liquid phase separation (LLPS) are found to interact intimately with membranous organelles (MOs). One major mode is the clustering of MOs by MLOs, such as the formation of clusters of synaptic vesicles at nerve terminals mediated by the synapsin-rich MLOs. Aqueous droplets, including complex coacervates and aqueous two-phase systems, have been plausible MLO-mimics to emulate or elucidate biological processes. However, neither of them can cluster lipid vesicles (LVs) like MLOs. In this work, we develop a synthetic droplet assembled from a combination of two different interactions underlying the formation of these two droplets, namely, associative and segregative interactions, which we call segregative-associative (SA) droplets. The SA droplets cluster and disperse LVs recapitulating the key functional features of synapsin condensates, which can be attributed to the weak electrostatic interaction environment provided by SA droplets. This work suggests LLPS with combined segregative and associative interactions as a possible route for synaptic clustering of lipid vesicles and highlights SA droplets as plausible MLO-mimics and models for studying and mimicking related cellular dynamics. © 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

Original language	English
Article number	e202313096
Journal	Angewandte Chemie International Edition
Volume	62
Issue number	45
Online published	20 Sept 2023
DOIs	https://doi.org/10.1002/anie.202313096
Publication status	Published - 6 Nov 2023
Externally published	Yes

Funding

This research is supported by the General Research Fund (Nos. 17306221, 17306820, and 17317322), National Natural Science Foundation of China/RGC Joint Research Scheme (N_HKU718/19), the NSFC Excellent Young Scientists Fund (Hong Kong and Macau) (21922816), and the Natural Science Foundation of Heilongjiang Province (LH2021H114). Q.C.L. was supported by the Hong Kong Scholars Program. Q.C.L., W.G. and H.C.S. were supported by the Health@InnoHK program of the Innovation Technology Commission of the Hong Kong SAR Government. H.C.S. was partially supported by the Croucher Foundation through the Croucher Senior Research Fellowship.

Research Keywords

Biomolecular Condensates
Lipid Vesicles
Liquid-Liquid Phase Separation
Membraneless Organelles
Synthetic Cell

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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abstract = "In eukaryotic cells, the membraneless organelles (MLOs) formed via liquid-liquid phase separation (LLPS) are found to interact intimately with membranous organelles (MOs). One major mode is the clustering of MOs by MLOs, such as the formation of clusters of synaptic vesicles at nerve terminals mediated by the synapsin-rich MLOs. Aqueous droplets, including complex coacervates and aqueous two-phase systems, have been plausible MLO-mimics to emulate or elucidate biological processes. However, neither of them can cluster lipid vesicles (LVs) like MLOs. In this work, we develop a synthetic droplet assembled from a combination of two different interactions underlying the formation of these two droplets, namely, associative and segregative interactions, which we call segregative-associative (SA) droplets. The SA droplets cluster and disperse LVs recapitulating the key functional features of synapsin condensates, which can be attributed to the weak electrostatic interaction environment provided by SA droplets. This work suggests LLPS with combined segregative and associative interactions as a possible route for synaptic clustering of lipid vesicles and highlights SA droplets as plausible MLO-mimics and models for studying and mimicking related cellular dynamics. {\textcopyright} 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.",

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AU - Li, Qingchuan

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AU - Guo, Wei

AU - Cao, Yang

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AU - Chen, Dairong

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AB - In eukaryotic cells, the membraneless organelles (MLOs) formed via liquid-liquid phase separation (LLPS) are found to interact intimately with membranous organelles (MOs). One major mode is the clustering of MOs by MLOs, such as the formation of clusters of synaptic vesicles at nerve terminals mediated by the synapsin-rich MLOs. Aqueous droplets, including complex coacervates and aqueous two-phase systems, have been plausible MLO-mimics to emulate or elucidate biological processes. However, neither of them can cluster lipid vesicles (LVs) like MLOs. In this work, we develop a synthetic droplet assembled from a combination of two different interactions underlying the formation of these two droplets, namely, associative and segregative interactions, which we call segregative-associative (SA) droplets. The SA droplets cluster and disperse LVs recapitulating the key functional features of synapsin condensates, which can be attributed to the weak electrostatic interaction environment provided by SA droplets. This work suggests LLPS with combined segregative and associative interactions as a possible route for synaptic clustering of lipid vesicles and highlights SA droplets as plausible MLO-mimics and models for studying and mimicking related cellular dynamics. © 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Synthetic Membraneless Droplets for Synaptic-Like Clustering of Lipid Vesicles

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