@article{14442,
abstract = {In the presence of an obstacle, active particles condensate into a surface “wetting” layer due to persistent motion. If the obstacle is asymmetric, a rectification current arises in addition to wetting. Asymmetric geometries are therefore commonly used to concentrate microorganisms like bacteria and sperms. However, most studies neglect the fact that biological active matter is diverse, composed of individuals with distinct self-propulsions. Using simulations, we study a mixture of “fast” and “slow” active Brownian disks in two dimensions interacting with large half-disk obstacles. With this prototypical obstacle geometry, we analyze how the stationary collective behavior depends on the degree of self-propulsion “diversity,” defined as proportional to the difference between the self-propulsion speeds, while keeping the average self-propulsion speed fixed. A wetting layer rich in fast particles arises. The rectification current is amplified by speed diversity due to a superlinear dependence of rectification on self-propulsion speed, which arises from cooperative effects. Thus, the total rectification current cannot be obtained from an effective one-component active fluid with the same average self-propulsion speed, highlighting the importance of considering diversity in active matter.},
author = {Rojas Vega, Mauricio Nicolas and De Castro, Pablo and Soto, Rodrigo},
issn = {1292-895X},
journal = {The European Physical Journal E},
number = {10},
publisher = {Springer Nature},
title = {{Mixtures of self-propelled particles interacting with asymmetric obstacles}},
doi = {10.1140/epje/s10189-023-00354-y},
volume = {46},
year = {2023},
}
@misc{14472,
abstract = {Data related to the following paper:
"Stress granules plug and stabilize damaged endolysosomal membranes" (https://doi.org/10.1038/s41586-023-06726-w)
Abstract:
Endomembrane damage represents a form of stress that is detrimental for eukaryotic cells. To cope with this threat, cells possess mechanisms that repair the damage and restore cellular homeostasis. Endomembrane damage also results in organelle instability and the mechanisms by which cells stabilize damaged endomembranes to enable membrane repair remains unknown. In this work we use a minimal coarse-grained molecular dynamics system to explore how lipid vesicles undergoing poration in a protein-rich medium can be plugged and stabilised by condensate formation. The solution of proteins in and out of the vesicle is described by beads dispersed in implicit solvent. The membrane is described as a one-bead-thick fluid elastic layer of mechanical properties that mimic biological membranes. We tune the interactions between solution beads in the different compartments to capture the differences between the cytoplasmic and endosomal protein solutions and explore how the system responds to different degrees of membrane poration. We find that, in the right interaction regime, condensates form rapidly at the damage site upon solution mixing and act as a plug that prevents futher mixing and destabilisation of the vesicle. Further, when the condensate can interact with the membrane (wetting interactions) we find that it mediates pore sealing and membrane repair. This research is part of the work published in "Stress granules plug and stabilize damaged endolysosomal membranes", Bussi et al, Nature, 2023 - 10.1038/s41586-023-06726-w.},
author = {Vanhille-Campos, Christian Eduardo and Šarić, Anđela},
publisher = {Institute of Science and Technology Austria},
title = {{Stress granules plug and stabilize damaged endolysosomal membranes}},
doi = {10.15479/AT:ISTA:14472},
year = {2023},
}
@article{14610,
abstract = {Endomembrane damage represents a form of stress that is detrimental for eukaryotic cells1,2. To cope with this threat, cells possess mechanisms that repair the damage and restore cellular homeostasis3–7. Endomembrane damage also results in organelle instability and the mechanisms by which cells stabilize damaged endomembranes to enable membrane repair remains unknown. Here, by combining in vitro and in cellulo studies with computational modelling we uncover a biological function for stress granules whereby these biomolecular condensates form rapidly at endomembrane damage sites and act as a plug that stabilizes the ruptured membrane. Functionally, we demonstrate that stress granule formation and membrane stabilization enable efficient repair of damaged endolysosomes, through both ESCRT (endosomal sorting complex required for transport)-dependent and independent mechanisms. We also show that blocking stress granule formation in human macrophages creates a permissive environment for Mycobacterium tuberculosis, a human pathogen that exploits endomembrane damage to survive within the host.},
author = {Bussi, Claudio and Mangiarotti, Agustín and Vanhille-Campos, Christian Eduardo and Aylan, Beren and Pellegrino, Enrica and Athanasiadi, Natalia and Fearns, Antony and Rodgers, Angela and Franzmann, Titus M. and Šarić, Anđela and Dimova, Rumiana and Gutierrez, Maximiliano G.},
issn = {1476-4687},
journal = {Nature},
pages = {1062--1069},
publisher = {Springer Nature},
title = {{Stress granules plug and stabilize damaged endolysosomal membranes}},
doi = {10.1038/s41586-023-06726-w},
volume = {623},
year = {2023},
}
@article{14655,
abstract = {The kinetics of the assembly of semiflexible filaments through end-to-end annealing is key to the structure of the cytoskeleton, but is not understood. We analyze this problem through scaling theory and simulations, and uncover a regime where filaments’ ends find each other through bending fluctuations without the need for the whole filament to diffuse. This results in a very substantial speedup of assembly in physiological regimes, and could help with understanding the dynamics of actin and intermediate filaments in biological processes such as wound healing and cell division.},
author = {Sorichetti, Valerio and Lenz, Martin},
issn = {1079-7114},
journal = {Physical Review Letters},
number = {22},
publisher = {American Physical Society},
title = {{Transverse fluctuations control the assembly of semiflexible filaments}},
doi = {10.1103/PhysRevLett.131.228401},
volume = {131},
year = {2023},
}
@article{14782,
abstract = {The actin cortex is a complex cytoskeletal machinery that drives and responds to changes in cell shape. It must generate or adapt to plasma membrane curvature to facilitate diverse functions such as cell division, migration, and phagocytosis. Due to the complex molecular makeup of the actin cortex, it remains unclear whether actin networks are inherently able to sense and generate membrane curvature, or whether they rely on their diverse binding partners to accomplish this. Here, we show that curvature sensing is an inherent capability of branched actin networks nucleated by Arp2/3 and VCA. We develop a robust method to encapsulate actin inside giant unilamellar vesicles (GUVs) and assemble an actin cortex at the inner surface of the GUV membrane. We show that actin forms a uniform and thin cortical layer when present at high concentration and distinct patches associated with negative membrane curvature at low concentration. Serendipitously, we find that the GUV production method also produces dumbbell-shaped GUVs, which we explain using mathematical modeling in terms of membrane hemifusion of nested GUVs. We find that branched actin networks preferentially assemble at the neck of the dumbbells, which possess a micrometer-range convex curvature comparable with the curvature of the actin patches found in spherical GUVs. Minimal branched actin networks can thus sense membrane curvature, which may help mammalian cells to robustly recruit actin to curved membranes to facilitate diverse cellular functions such as cytokinesis and migration.},
author = {Baldauf, Lucia and Frey, Felix F and Arribas Perez, Marcos and Idema, Timon and Koenderink, Gijsje H.},
issn = {0006-3495},
journal = {Biophysical Journal},
keywords = {Biophysics},
number = {11},
pages = {2311--2324},
publisher = {Elsevier},
title = {{Branched actin cortices reconstituted in vesicles sense membrane curvature}},
doi = {10.1016/j.bpj.2023.02.018},
volume = {122},
year = {2023},
}
@article{14788,
abstract = {Eukaryotic cells use clathrin-mediated endocytosis to take up a large range of extracellular cargo. During endocytosis, a clathrin coat forms on the plasma membrane, but it remains controversial when and how it is remodeled into a spherical vesicle.
Here, we use 3D superresolution microscopy to determine the precise geometry of the clathrin coat at large numbers of endocytic sites. Through pseudo-temporal sorting, we determine the average trajectory of clathrin remodeling during endocytosis. We find that clathrin coats assemble first on flat membranes to 50% of the coat area before they become rapidly and continuously bent, and this mechanism is confirmed in three cell lines. We introduce the cooperative curvature model, which is based on positive feedback for curvature generation. It accurately describes the measured shapes and dynamics of the clathrin coat and could represent a general mechanism for clathrin coat remodeling on the plasma membrane.},
author = {Mund, Markus and Tschanz, Aline and Wu, Yu-Le and Frey, Felix F and Mehl, Johanna L. and Kaksonen, Marko and Avinoam, Ori and Schwarz, Ulrich S. and Ries, Jonas},
issn = {1540-8140},
journal = {Journal of Cell Biology},
keywords = {Cell Biology},
number = {3},
publisher = {Rockefeller University Press},
title = {{Clathrin coats partially preassemble and subsequently bend during endocytosis}},
doi = {10.1083/jcb.202206038},
volume = {222},
year = {2023},
}
@article{14831,
abstract = {Catalysis, the acceleration of product formation by a substance that is left unchanged, typically results from multiple elementary processes, including diffusion of the reactants toward the catalyst, chemical steps, and release of the products. While efforts to design catalysts are often focused on accelerating the chemical reaction on the catalyst, catalysis is a global property of the catalytic cycle that involves all processes. These are controlled by both intrinsic parameters such as the composition and shape of the catalyst and extrinsic parameters such as the concentration of the chemical species at play. We examine here the conditions that catalysis imposes on the different steps of a reaction cycle and the respective role of intrinsic and extrinsic parameters of the system on the emergence of catalysis by using an approach based on first-passage times. We illustrate this approach for various decompositions of a catalytic cycle into elementary steps, including non-Markovian decompositions, which are useful when the presence and nature of intermediate states are a priori unknown. Our examples cover different types of reactions and clarify the constraints on elementary steps and the impact of species concentrations on catalysis.},
author = {Sakref, Yann and Muñoz Basagoiti, Maitane and Zeravcic, Zorana and Rivoire, Olivier},
issn = {1520-5207},
journal = {The Journal of Physical Chemistry B},
keywords = {Materials Chemistry, Surfaces, Coatings and Films, Physical and Theoretical Chemistry},
number = {51},
pages = {10950--10959},
publisher = {American Chemical Society},
title = {{On kinetic constraints that catalysis imposes on elementary processes}},
doi = {10.1021/acs.jpcb.3c04627},
volume = {127},
year = {2023},
}
@misc{15027,
abstract = {This data repository underpins the paper, published in PNAS (doi pending) and bioarxiv (doi: https://doi.org/10.1101/2023.07.05.547777).},
author = {Curk, Samo},
publisher = {Figshare},
title = {{aggregation_data}},
year = {2023},
}
@article{11340,
abstract = {Like-charge attraction, driven by ionic correlations, challenges our understanding of electrostatics both in soft and hard matter. For two charged planar surfaces confining counterions and water, we prove that, even at relatively low correlation strength, the relevant physics is the ground-state one, oblivious of fluctuations. Based on this, we derive a simple and accurate interaction pressure that fulfills known exact requirements and can be used as an effective potential. We test this equation against implicit-solvent Monte Carlo simulations and against explicit-solvent simulations of cement and several types of clays. We argue that water destructuring under nanometric confinement drastically reduces dielectric screening, enhancing ionic correlations. Our equation of state at reduced permittivity therefore explains the exotic attractive regime reported for these materials, even in the absence of multivalent counterions.},
author = {Palaia, Ivan and Goyal, Abhay and Del Gado, Emanuela and Šamaj, Ladislav and Trizac, Emmanuel},
issn = {1520-5207},
journal = {Journal of Physical Chemistry B},
number = {16},
pages = {3143--3149},
publisher = {American Chemical Society},
title = {{Like-charge attraction at the nanoscale: Ground-state correlations and water destructuring}},
doi = {10.1021/acs.jpcb.2c00028},
volume = {126},
year = {2022},
}
@article{11400,
abstract = {By varying the concentration of molecules in the cytoplasm or on the membrane, cells can induce the formation of condensates and liquid droplets, similar to phase separation. Their thermodynamics, much studied, depends on the mutual interactions between microscopic constituents. Here, we focus on the kinetics and size control of 2D clusters, forming on membranes. Using molecular dynamics of patchy colloids, we model a system of two species of proteins, giving origin to specific heterotypic bonds. We find that concentrations, together with valence and bond strength, control both the size and the growth time rate of the clusters. In particular, if one species is in large excess, it gradually saturates the binding sites of the other species; the system then becomes kinetically arrested and cluster coarsening slows down or stops, thus yielding effective size selection. This phenomenology is observed both in solid and fluid clusters, which feature additional generic homotypic interactions and are reminiscent of the ones observed on biological membranes.},
author = {Palaia, Ivan and Šarić, Anđela},
issn = {1089-7690},
journal = {The Journal of Chemical Physics},
keywords = {Physical and Theoretical Chemistry, General Physics and Astronomy},
number = {19},
publisher = {AIP Publishing},
title = {{Controlling cluster size in 2D phase-separating binary mixtures with specific interactions}},
doi = {10.1063/5.0087769},
volume = {156},
year = {2022},
}
@article{11841,
abstract = {Primary nucleation is the fundamental event that initiates the conversion of proteins from their normal physiological forms into pathological amyloid aggregates associated with the onset and development of disorders including systemic amyloidosis, as well as the neurodegenerative conditions Alzheimer’s and Parkinson’s diseases. It has become apparent that the presence of surfaces can dramatically modulate nucleation. However, the underlying physicochemical parameters governing this process have been challenging to elucidate, with interfaces in some cases having been found to accelerate aggregation, while in others they can inhibit the kinetics of this process. Here we show through kinetic analysis that for three different fibril-forming proteins, interfaces affect the aggregation reaction mainly through modulating the primary nucleation step. Moreover, we show through direct measurements of the Gibbs free energy of adsorption, combined with theory and coarse-grained computer simulations, that overall nucleation rates are suppressed at high and at low surface interaction strengths but significantly enhanced at intermediate strengths, and we verify these regimes experimentally. Taken together, these results provide a quantitative description of the fundamental process which triggers amyloid formation and shed light on the key factors that control this process.},
author = {Toprakcioglu, Zenon and Kamada, Ayaka and Michaels, Thomas C.T. and Xie, Mengqi and Krausser, Johannes and Wei, Jiapeng and Šarić, Anđela and Vendruscolo, Michele and Knowles, Tuomas P.J.},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {31},
publisher = {National Academy of Sciences},
title = {{Adsorption free energy predicts amyloid protein nucleation rates}},
doi = {10.1073/pnas.2109718119},
volume = {119},
year = {2022},
}
@article{12108,
abstract = {The sequential exchange of filament composition to increase filament curvature was proposed as a mechanism for how some biological polymers deform and cut membranes. The relationship between the filament composition and its mechanical effect is lacking. We develop a kinetic model for the assembly of composite filaments that includes protein–membrane adhesion, filament mechanics and membrane mechanics. We identify the physical conditions for such a membrane remodeling and show this mechanism of sequential polymer assembly lowers the energetic barrier for membrane deformation.},
author = {Meadowcroft, Billie and Palaia, Ivan and Pfitzner, Anna Katharina and Roux, Aurélien and Baum, Buzz and Šarić, Anđela},
issn = {1079-7114},
journal = {Physical Review Letters},
number = {26},
publisher = {American Physical Society},
title = {{Mechanochemical rules for shape-shifting filaments that remodel membranes}},
doi = {10.1103/PhysRevLett.129.268101},
volume = {129},
year = {2022},
}
@article{12152,
abstract = {ESCRT-III filaments are composite cytoskeletal polymers that can constrict and cut cell membranes from the inside of the membrane neck. Membrane-bound ESCRT-III filaments undergo a series of dramatic composition and geometry changes in the presence of an ATP-consuming Vps4 enzyme, which causes stepwise changes in the membrane morphology. We set out to understand the physical mechanisms involved in translating the changes in ESCRT-III polymer composition into membrane deformation. We have built a coarse-grained model in which ESCRT-III polymers of different geometries and mechanical properties are allowed to copolymerise and bind to a deformable membrane. By modelling ATP-driven stepwise depolymerisation of specific polymers, we identify mechanical regimes in which changes in filament composition trigger the associated membrane transition from a flat to a buckled state, and then to a tubule state that eventually undergoes scission to release a small cargo-loaded vesicle. We then characterise how the location and kinetics of polymer loss affects the extent of membrane deformation and the efficiency of membrane neck scission. Our results identify the near-minimal mechanical conditions for the operation of shape-shifting composite polymers that sever membrane necks.},
author = {Jiang, Xiuyun and Harker-Kirschneck, Lena and Vanhille-Campos, Christian Eduardo and Pfitzner, Anna-Katharina and Lominadze, Elene and Roux, Aurélien and Baum, Buzz and Šarić, Anđela},
issn = {1553-7358},
journal = {PLOS Computational Biology},
keywords = {Computational Theory and Mathematics, Cellular and Molecular Neuroscience, Genetics, Molecular Biology, Ecology, Modeling and Simulation, Ecology, Evolution, Behavior and Systematics},
number = {10},
publisher = {Public Library of Science},
title = {{Modelling membrane reshaping by staged polymerization of ESCRT-III filaments}},
doi = {10.1371/journal.pcbi.1010586},
volume = {18},
year = {2022},
}
@article{12251,
abstract = {Amyloid formation is linked to devastating neurodegenerative diseases, motivating detailed studies of the mechanisms of amyloid formation. For Aβ, the peptide associated with Alzheimer’s disease, the mechanism and rate of aggregation have been established for a range of variants and conditions in vitro and in bodily fluids. A key outstanding question is how the relative stabilities of monomers, fibrils and intermediates affect each step in the fibril formation process. By monitoring the kinetics of aggregation of Aβ42, in the presence of urea or guanidinium hydrochloride (GuHCl), we here determine the rates of the underlying microscopic steps and establish the importance of changes in relative stability induced by the presence of denaturant for each individual step. Denaturants shift the equilibrium towards the unfolded state of each species. We find that a non-ionic denaturant, urea, reduces the overall aggregation rate, and that the effect on nucleation is stronger than the effect on elongation. Urea reduces the rate of secondary nucleation by decreasing the coverage of fibril surfaces and the rate of nucleus formation. It also reduces the rate of primary nucleation, increasing its reaction order. The ionic denaturant, GuHCl, accelerates the aggregation at low denaturant concentrations and decelerates the aggregation at high denaturant concentrations. Below approximately 0.25 M GuHCl, the screening of repulsive electrostatic interactions between peptides by the charged denaturant dominates, leading to an increased aggregation rate. At higher GuHCl concentrations, the electrostatic repulsion is completely screened, and the denaturing effect dominates. The results illustrate how the differential effects of denaturants on stability of monomer, oligomer and fibril translate to differential effects on microscopic steps, with the rate of nucleation being most strongly reduced.},
author = {Weiffert, Tanja and Meisl, Georg and Curk, Samo and Cukalevski, Risto and Šarić, Anđela and Knowles, Tuomas P. J. and Linse, Sara},
issn = {1662-453X},
journal = {Frontiers in Neuroscience},
keywords = {General Neuroscience},
publisher = {Frontiers Media},
title = {{Influence of denaturants on amyloid β42 aggregation kinetics}},
doi = {10.3389/fnins.2022.943355},
volume = {16},
year = {2022},
}