Coacervate-pore Complexes for Selective Molecular Transport and Dynamic Reconfiguration

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Nov 20

PMID 39567561

Authors

Hao Wang

Hui Zhuang

Wenjing Tang

Jun Zhu

Wei Zhu

Lingxiang Jiang

Affiliations

Soon will be listed here.

Abstract

Despite surging interests on liquid-state coacervates and condensates, confinement within solid-state pores for selective permeation remains an unexplored area. Drawing inspiration from nuclear pore complexes (NPCs), we design and construct coacervate-pore complexes (CPCs) with regulatable permeability. We demonstrate universal CPC formation across 19 coacervate systems and 5 pore types, where capillarity drives the spontaneous imbibition of coacervate droplets into dispersed or interconnected pores. CPCs regulate through-pore transport by forming a fluidic network that modulates guest molecule permeability based on guest-coacervate affinity, mimicking NPC selectivity. While solid constructs of NPC mimicries are limited by spatial fixation of polymer chains, CPCs of a liquid nature feature dynamic healing and rapid phase transitioning for permeability recovery and regulation, respectively. Looking forward, we expect the current work to establish a basis for developing liquid-based NPC analogs using a large pool of synthetic coacervates and biomolecular condensates.

References

Patel A, Lee H, Jawerth L, Maharana S, Jahnel M, Hein M . A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation. Cell. 2015; 162(5):1066-77. DOI: 10.1016/j.cell.2015.07.047. View

Su Q, Mehta S, Zhang J . Liquid-liquid phase separation: Orchestrating cell signaling through time and space. Mol Cell. 2021; 81(20):4137-4146. PMC: 8541918. DOI: 10.1016/j.molcel.2021.09.010. View

Schlenoff J . Zwitteration: coating surfaces with zwitterionic functionality to reduce nonspecific adsorption. Langmuir. 2014; 30(32):9625-36. PMC: 4140545. DOI: 10.1021/la500057j. View

Driessen R, Sitters G, Laurens N, Moolenaar G, Wuite G, Goosen N . Effect of temperature on the intrinsic flexibility of DNA and its interaction with architectural proteins. Biochemistry. 2014; 53(41):6430-8. PMC: 5451147. DOI: 10.1021/bi500344j. View

Sponchioni M, Rodrigues Bassam P, Moscatelli D, Arosio P, Capasso Palmiero U . Biodegradable zwitterionic nanoparticles with tunable UCST-type phase separation under physiological conditions. Nanoscale. 2019; 11(35):16582-16591. DOI: 10.1039/c9nr04311j. View

Taylor N, Wei M, Stone H, Brangwynne C . Quantifying Dynamics in Phase-Separated Condensates Using Fluorescence Recovery after Photobleaching. Biophys J. 2019; 117(7):1285-1300. PMC: 6818185. DOI: 10.1016/j.bpj.2019.08.030. View

Kowalczyk S, Kapinos L, Blosser T, Magalhaes T, van Nies P, Lim R . Single-molecule transport across an individual biomimetic nuclear pore complex. Nat Nanotechnol. 2011; 6(7):433-8. DOI: 10.1038/nnano.2011.88. View

Schmidt H, Gorlich D . Transport Selectivity of Nuclear Pores, Phase Separation, and Membraneless Organelles. Trends Biochem Sci. 2015; 41(1):46-61. DOI: 10.1016/j.tibs.2015.11.001. View

Jawerth L, Fischer-Friedrich E, Saha S, Wang J, Franzmann T, Zhang X . Protein condensates as aging Maxwell fluids. Science. 2020; 370(6522):1317-1323. DOI: 10.1126/science.aaw4951. View

10.

Yu M, Heidari M, Mikhaleva S, Tan P, Mingu S, Ruan H . Visualizing the disordered nuclear transport machinery in situ. Nature. 2023; 617(7959):162-169. PMC: 10156602. DOI: 10.1038/s41586-023-05990-0. View

11.

Rush C, Jiang Z, Tingey M, Feng F, Yang W . Unveiling the complexity: assessing models describing the structure and function of the nuclear pore complex. Front Cell Dev Biol. 2023; 11:1245939. PMC: 10591098. DOI: 10.3389/fcell.2023.1245939. View

12.

Huang K, Szleifer I . Design of Multifunctional Nanogate in Response to Multiple External Stimuli Using Amphiphilic Diblock Copolymer. J Am Chem Soc. 2017; 139(18):6422-6430. DOI: 10.1021/jacs.7b02057. View

13.

Mountain G, Keating C . Formation of Multiphase Complex Coacervates and Partitioning of Biomolecules within them. Biomacromolecules. 2019; 21(2):630-640. DOI: 10.1021/acs.biomac.9b01354. View

14.

Xu C, Martin N, Li M, Mann S . Living material assembly of bacteriogenic protocells. Nature. 2022; 609(7929):1029-1037. DOI: 10.1038/s41586-022-05223-w. View

15.

Ng S, Guttler T, Gorlich D . Recapitulation of selective nuclear import and export with a perfectly repeated 12mer GLFG peptide. Nat Commun. 2021; 12(1):4047. PMC: 8245513. DOI: 10.1038/s41467-021-24292-5. View

16.

Olsen C, Lee H, Marky L . Unfolding thermodynamics of intramolecular G-quadruplexes: base sequence contributions of the loops. J Phys Chem B. 2008; 113(9):2587-95. DOI: 10.1021/jp806853n. View

17.

Banani S, Lee H, Hyman A, Rosen M . Biomolecular condensates: organizers of cellular biochemistry. Nat Rev Mol Cell Biol. 2017; 18(5):285-298. PMC: 7434221. DOI: 10.1038/nrm.2017.7. View

18.

Cowburn D, Rout M . Improving the hole picture: towards a consensus on the mechanism of nuclear transport. Biochem Soc Trans. 2023; 51(2):871-886. PMC: 10212546. DOI: 10.1042/BST20220494. View

19.

Ketterer P, Ananth A, Laman Trip D, Mishra A, Bertosin E, Ganji M . DNA origami scaffold for studying intrinsically disordered proteins of the nuclear pore complex. Nat Commun. 2018; 9(1):902. PMC: 5834454. DOI: 10.1038/s41467-018-03313-w. View

20.

Wei M, Elbaum-Garfinkle S, Holehouse A, Chen C, Feric M, Arnold C . Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles. Nat Chem. 2017; 9(11):1118-1125. PMC: 9719604. DOI: 10.1038/nchem.2803. View