Exploring the Theoretical Propensity for Liquid-Liquid Phase Separation in the Organization of Golgi Matrix Proteins DOI Creative Commons
Luís F.S. Mendes, Carolina Boschi Gimenes, Emanuel Kava

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 22, 2023

Abstract The Golgi apparatus is a critical organelle in protein sorting and lipid metabolism. Characterized by its stacked, flattened cisternal structure, the exhibits distinct polarity with cis - trans -faces orchestrating various maturation transport processes. At heart of structural integrity organization are Matrix Proteins (GMPs), predominantly comprising Golgins GRASPs. These proteins contribute to this organelle’s unique stacked polarized structure ensure precise localization Golgi-resident enzymes, which crucial for accurate processing. Despite over century research since discovery, architecture’s intricate mechanisms still need be fully understood. Here, we demonstrate that GMPs present significant tendency form biocondensates through Liquid-Liquid Phase Separation (LLPS) across different Eukaryotic lineages. Moreover, validated experimentally members GRASP family also exhibit strong LLPS. Our findings offer new perspective on possible roles disorder LLPS organization.

Language: Английский

Biomolecular Condensates in Contact with Membranes DOI
Agustín Mangiarotti, Rumiana Dimova

Annual Review of Biophysics, Journal Year: 2024, Volume and Issue: 53(1), P. 319 - 341

Published: Feb. 16, 2024

Biomolecular condensates are highly versatile membraneless organelles involved in a plethora of cellular processes. Recent years have witnessed growing evidence the interaction these droplets with membrane-bound structures. Condensates' adhesion to membranes can cause their mutual molding and regulation, is fundamental relevance intracellular organization communication, organelle remodeling, embryogenesis, phagocytosis. In this article, we review advances understanding membrane-condensate interactions, focus on vitro models. These minimal systems allow precise characterization tuning material properties both provide workbench for visualizing resulting morphologies quantifying interactions. interactions give rise diverse biologically relevant phenomena, such as molecular-level restructuring membrane, nano- microscale ruffling condensate-membrane interface, coupling protein lipid phases.

Language: Английский

Citations

26
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

30
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

14
Scanning probe microscopy elucidates gelation and rejuvenation of biomolecular condensates DOI Creative Commons
Aida Naghilou, Oskar Armbruster, Alireza Mashaghi

et al.

Cell Reports Physical Science, Journal Year: 2025, Volume and Issue: unknown, P. 102430 - 102430

Published: Feb. 1, 2025

Language: Английский

Citations

1
Protein–membrane interactions: sensing and generating curvature DOI
David H. Johnson,

Orianna H. Kou,

Nicoletta Bouzos

et al.

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(5), P. 401 - 416

Published: March 19, 2024

Language: Английский

Citations

8
Adhesion energy controls lipid binding-mediated endocytosis DOI Creative Commons
Raluca Groza,

Kita Valerie Schmidt,

Paul Markus Müller

et al.

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

Published: March 29, 2024

Abstract Several bacterial toxins and viruses can deform membranes through multivalent binding to lipids for clathrin-independent endocytosis. However, it remains unclear, how membrane deformation endocytic internalization are mechanistically linked. Here we show that many lipid-binding virions induce endocytosis, suggesting a common mechanism based on lipid by globular particles. We create synthetic cellular system consisting of lipid-anchored receptor in the form GPI-anchored anti-GFP nanobodies binder exposing 180 regularly-spaced GFP molecules its surface. these globular, 40 nm diameter, particles bind cells expressing receptor, plasma upon adhesion become endocytosed manner. explore role energy endocytosis using receptors with affinities varying over 7 orders magnitude. Using this system, find once threshold is overcome allow deformation, occurs reliably. Multivalent, binding-induced binders thus sufficient occur suggest common, purely biophysical mediated pathogens.

Language: Английский

Citations

8
Lipid packing and cholesterol content regulate membrane wetting and remodeling by biomolecular condensates DOI Creative Commons
Agustín Mangiarotti, Elias Sabri,

Kita Valerie Schmidt

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 20, 2025

Abstract Biomolecular condensates play a central role in cellular processes by interacting with membranes driving wetting transitions and inducing mutual remodeling. While are known to locally alter membrane properties such as lipid packing hydration, it remains unclear how composition phase state turn affect condensate affinity. Here, we show that is not only the itself, but rather degree of determines affinity for membranes. Increasing chain length, saturation, or cholesterol content, enhances packing, thereby decreasing interaction. This regulatory mechanism consistent across various condensate-membrane systems, highlighting critical interface. In addition, protein adsorption promotes extensive remodeling, including formation tubes double-membrane sheets. Our findings reveal which fine-tunes wetting, its potential impact on functions organelle interactions.

Language: Английский

Citations

0
The mechanobiology of biomolecular condensates DOI Creative Commons
Neus Sanfeliu-Cerdán, Michael Krieg

Biophysics Reviews, Journal Year: 2025, Volume and Issue: 6(1)

Published: March 1, 2025

The central goal of mechanobiology is to understand how the mechanical forces and material properties organelles, cells, tissues influence biological processes functions. Since first description biomolecular condensates, it was hypothesized that they obtain are tuned their functions inside cells. Thus, represent an intriguing playground for mechanobiology. idea condensates exhibit diverse adaptive highlights need different states respond external whether these responses linked physiological roles within cell. For example, liquids buffer dissipate, while solids store transmit stress, relaxation time a viscoelastic can act as frequency filter. Hence, liquid-solid transition condensate in force transmission pathway determine signals transduced in-between affecting differentiation, neuronal network dynamics, behavior stimuli. Here, we review our current understanding molecular drivers rigidity phase transitions set forth complex cellular environment. We will then summarize technical advancements were necessary insights into rich fascinating finally, highlight recent examples connection specific Our provide comprehensive summary field on cells harness regulate mechanics achieve

Language: Английский

Citations

0
Lipid packing and cholesterol content regulate membrane wetting by biomolecular condensates DOI Creative Commons
Agustín Mangiarotti, Elias Sabri,

Kita Valerie Schmidt

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

Abstract Biomolecular condensates play a pivotal role in cellular processes by interacting with membranes and leading to wetting transitions mutual remodeling. Using combination of hyperspectral imaging, phasor analysis, fluid-elastic parameter measurements, we investigated how membrane lipid packing affects condensate wetting. Our results show that it is not only the phase state, but rather degree determines affinity for membranes. Increasing chain length or cholesterol content enhances packing, thereby decreasing affinity. This regulatory mechanism consistent across various condensate-membrane systems, underscoring critical interface. Additionally, protein adsorption promotes extensive remodeling, including tube double-membrane sheet formation. work provides novel which composition fine-tunes wetting, highlighting its potential impact on functions organelle interactions.

Language: Английский

Citations

3
Exploring the structural stability of hemoglobin in DBU-based ionic liquids: Insights from spectroscopic investigations DOI

K.J. Jisha,

Ramesh L. Gardas

Journal of Molecular Liquids, Journal Year: 2023, Volume and Issue: 388, P. 122837 - 122837

Published: Aug. 15, 2023

Language: Английский

Citations

7