Photoswitchable Endocytosis of Biomolecular Condensates in Giant Vesicles DOI
Agustín Mangiarotti, Mina Aleksanyan, Macarena Siri

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(23)

Published: April 6, 2024

Abstract Interactions between membranes and biomolecular condensates can give rise to complex phenomena such as wetting transitions, mutual remodeling, endocytosis. In this study, light‐triggered manipulation of condensate engulfment is demonstrated using giant vesicles containing photoswitchable lipids. UV irradiation increases the membrane area, which be stored in nanotubes. When contact with a droplet, light triggers rapid endocytosis, reverted by blue light. The affinity protein‐rich reversibility processes quantified from confocal microscopy images. degree photo‐induced engulfment, whether partial or complete, depends on vesicle excess area relative sizes condensates. Theoretical estimates suggest that utilizing light‐induced increase vesicle‐condensate adhesion interface energetically more favorable than energy gain folding into invaginations tubes. overall findings demonstrate membrane‐condensate interactions easily quickly modulated via light, providing versatile system for building platforms control cellular events design intelligent drug delivery systems cell repair.

Language: Английский

Interfacing Coacervates with Membranes: From Artificial Organelles and Hybrid Protocells to Intracellular Delivery DOI Creative Commons
Tiemei Lu, Sadaf Javed, Claudia Bonfio

et al.

Small Methods, Journal Year: 2023, Volume and Issue: 7(12)

Published: June 24, 2023

Abstract Compartmentalization is crucial for the functioning of cells. Membranes enclose and protect cell, regulate transport molecules entering exiting organize cellular machinery in subcompartments. In addition, membraneless condensates, or coacervates, offer dynamic compartments that act as biomolecular storage centers, organizational hubs, reaction crucibles. Emerging evidence shows phase‐separated bodies cell are involved a wide range functional interactions with membranes, leading to transmembrane signaling, membrane remodeling, intracellular transport, vesicle formation. Such interplay between droplets membranes also offers many potential benefits artificial cells, shown by recent studies involving coacervates liposomes. Depending on relative sizes interaction strength can serve organelles inside liposomes, templates assembly hybrid formation, remodelers tubulation possibly division, finally, cargo containers delivery biomolecules across endocytosis direct crossing. Here, experimental examples each these functions reviewed underlying physicochemical principles possible future applications discussed.

Language: Английский

Citations

27
Peptide-Based Coacervate Protocells with Cytoprotective Metal–Phenolic Network Membranes DOI
Linli Jiang, Yiwei Zeng, Hui Li

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(44), P. 24108 - 24115

Published: Oct. 3, 2023

Protocells have garnered considerable attention from cell biologists, materials scientists, and synthetic biologists. Phase-separating coacervate microdroplets emerged as a promising cytomimetic model because they can internalize concentrate components dilute surrounding environments. However, the membrane-free nature of such coacervates leads to coalescence into bulk phase, phenomenon that is not representative cells are designed mimic. Herein, we develop membranized peptide (PC) with oppositely charged oligopeptides molecularly crowded cytosol metal–phenolic network (MPN) coating membrane. The hybrid protocell efficiently internalizes various bioactive macromolecules (e.g., bovine serum albumin immunoglobulin G) (>90%) while also resisting radicals due semipermeable cytoprotective Notably, resultant PC@MPNs capable anabolic cascade reactions remain in discrete protocellular populations without coalescence. Finally, demonstrate MPN membrane be postfunctionalized functional molecules folic acid fluorescence dye) more closely resemble actual complex membranes, recognition molecules, which allows for drug delivery. This membrane-bound cytosolic structure paves way innovative structural complexity.

Language: Английский

Citations

24
Controlled Supramolecular Polymerization via Bioinspired, Liquid–Liquid Phase Separation of Monomers DOI
Satyajit Patra, Sushmitha Chandrabhas, Shikha Dhiman

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(18), P. 12577 - 12586

Published: April 29, 2024

Dynamic supramolecular assemblies, driven by noncovalent interactions, pervade the biological realm. In synthetic domain, their counterparts, polymers, endowed with remarkable self-repair and adaptive traits, are often realized through bioinspired designs. Recently, controlled polymerization strategies have emerged, drawing inspiration from protein self-assembly. A burgeoning area of research involves mimicking liquid–liquid phase separation (LLPS) observed in proteins to create coacervate droplets recognizing significance cellular organization diverse functions. Herein, we introduce a novel perspective on coacervates, extending beyond established role biology as dynamic, membraneless phases enable structural control polymers. Drawing parallels cooperative growth amyloid fibrils LLPS, present metastable dormant monomer for polymerization. This is achieved via π-conjugated design that combines characteristics both coacervation its terminal ionic groups one-dimensional core. leads unique temporal resulting phase, which subsequently undergoes nucleation within droplets. In-depth spectroscopic microscopic characterization provides insights into evolution disordered ordered phases. Furthermore, modulate kinetics liquid-to-solid transformation achieve precise over invoke seeding droplets, showcasing living characteristics. Our work thus opens up new avenues exciting field polymerization, offering general principles synthesis precision self-assembled structures confined environments.

Language: Английский

Citations

15
Probing the surface charge of condensates using microelectrophoresis DOI Creative Commons
Merlijn H. I. van Haren, Brent S. Visser, Evan Spruijt

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 26, 2024

Abstract Biomolecular condensates play an important role in cellular organization. Coacervates are commonly used models that mimic the physicochemical properties of biomolecular condensates. The surface plays a key governing molecular exchange between condensates, accumulation species at interface, and stability against coalescence. However, most properties, including charge zeta potential, remain poorly characterized understood. potential coacervates is often measured using laser doppler electrophoresis, which assumes size-independent electrophoretic mobility. Here, we show this assumption incorrect for liquid-like present alternative method to study mobility vitro condensate by microelectrophoresis single-particle tracking. have size-dependent mobility, originating from their fluid nature, well-defined calculated. Interestingly, measurements reveal polylysine chains enriched polylysine/polyaspartic acid complex coacervates, causes negatively charged protein ɑ-synuclein adsorb accumulate interface. Addition ATP inverts charge, displaces may help suppress its interface-catalyzed aggregation. Together, these findings how can be altered, making platform combined with automated tracking promising characterization technique both coacervate protocells.

Language: Английский

Citations

13
Biomolecular condensates mediate bending and scission of endosome membranes DOI Creative Commons
Yanning Wang, Shulin Li, Marcel Mokbel

et al.

Nature, Journal Year: 2024, Volume and Issue: 634(8036), P. 1204 - 1210

Published: Oct. 9, 2024

Multivesicular bodies are key endosomal compartments implicated in cellular quality control through their degradation of membrane-bound cargo proteins

Language: Английский

Citations

13
Cellular Uptake of Phase‐Separating Peptide Coacervates DOI Creative Commons

A. S. Shebanova,

Quentin Moana Perrin,

Kexin Zhu

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

Peptide coacervates self-assembling via liquid-liquid phase separation are appealing intracellular delivery vehicles of macromolecular therapeutics (proteins, DNA, mRNA) owing to their non-cytotoxicity, high encapsulation capacity, and efficient cellular uptake. However, the mechanisms by which these viscoelastic droplets cross membranes remain unknown. Here, using multimodal imaging, data analytics, biochemical inhibition assays, identify key steps enter cell. find that uptake follows a non-canonical pathway instead integrates essential features macropinocytosis phagocytosis, namely active remodeling actin cytoskeleton appearance filopodia-like protrusions. Experiments giant unilamellar vesicles show attach bounding membrane in charge- cholesterol-dependent manner but do not breach lipid bilayer barrier. Cell presence small molecule inhibitors - interfering with tubulin polymerization confirm role remodeling, most prominently evident electron microscopy imaging. These findings suggest peculiar internalization mechanism for viscoelastic, glassy coacervate combining non-specific fluids particulate phagocytosis. The broad implications this study will enable enhance efficacy utility coacervate-based strategies therapeutics.

Language: Английский

Citations

11
Interfacial energy-mediated bulk transport across artificial cell membranes DOI
Jiaqi Tian,

Mu-Yueh Chang,

Chen Chen

et al.

Nature Chemical Engineering, Journal Year: 2024, Volume and Issue: unknown

Published: July 4, 2024

Language: Английский

Citations

9
Polyelectrolyte-multivalent molecule complexes: physicochemical properties and applications DOI
Santiago E. Herrera, Maximiliano L. Agazzi,

Eugenia Apuzzo

et al.

Soft Matter, Journal Year: 2023, Volume and Issue: 19(11), P. 2013 - 2041

Published: Jan. 1, 2023

The complexation of polyelectrolytes with other oppositely charged structures gives rise to a great variety functional materials potential applications in wide spectrum technological fields. Depending on the assembly conditions, polyelectrolyte complexes can acquire different macroscopic configurations such as dense precipitates, nanosized colloids and liquid coacervates. In past 50 years, much progress has been achieved understand principles behind phase separation induced by interaction two aqueous solutions, especially for symmetric systems (systems which both polyions have similar molecular weight concentration). However, recent alternative building blocks small molecules (multivalent inorganic species, oligopeptides, oligoamines, among others) gained attention areas. this review, we discuss physicochemical characteristics formed multivalent molecules, putting special emphasis their similarities well-known polycation-polyanion complexes. addition, analyze these act versatile platforms various fields, biomedicine advanced engineering.

Language: Английский

Citations

22
Membrane reshaping by protein condensates DOI Creative Commons
Samsuzzoha Mondal, Tobias Baumgart

Biochimica et Biophysica Acta (BBA) - Biomembranes, Journal Year: 2023, Volume and Issue: 1865(3), P. 184121 - 184121

Published: Jan. 13, 2023

Language: Английский

Citations

19
Coacervate Microdroplets as Synthetic Protocells for Cell Mimicking and Signaling Communications DOI
Zefeng Wang, Min Zhang, Yan Zhou

et al.

Small Methods, Journal Year: 2023, Volume and Issue: 7(12)

Published: March 12, 2023

Synthetic protocells are minimal systems that mimic certain properties of natural cells and used to research the emergence life from a nonliving chemical network. Currently, coacervate microdroplets, which formed via liquid-liquid phase separation, receiving wide attention in context cell biology protocell research; these microdroplets notable because they can provide liquid-like compartment structures for biochemical reactions by creating highly macromolecular crowded local environments. In this review, an overview recent on formation through separation; design coacervate-based stimuli-responsive protocells, multichamber membranized protocells; their behaviors, is provided. The simplified models with precisely defined tunable compositions advance understanding requirements cellular structure function. Efforts then discussed establish signal communication consortia, as fundamental feature coordinates matter exchanges energy fluxes dynamically space time. Finally, some perspectives challenges future developments synthetic biomimetic science biomedical applications

Language: Английский

Citations

19