@article{15001,
abstract = {Self-replication of amyloid fibrils via secondary nucleation is an intriguing physicochemical phenomenon in which existing fibrils catalyze the formation of their own copies. The molecular events behind this fibril surface-mediated process remain largely inaccessible to current structural and imaging techniques. Using statistical mechanics, computer modeling, and chemical kinetics, we show that the catalytic structure of the fibril surface can be inferred from the aggregation behavior in the presence and absence of a fibril-binding inhibitor. We apply our approach to the case of Alzheimer’s A
amyloid fibrils formed in the presence of proSP-C Brichos inhibitors. We find that self-replication of A
fibrils occurs on small catalytic sites on the fibril surface, which are far apart from each other, and each of which can be covered by a single Brichos inhibitor.},
author = {Curk, Samo and Krausser, Johannes and Meisl, Georg and Frenkel, Daan and Linse, Sara and Michaels, Thomas C.T. and Knowles, Tuomas P.J. and Šarić, Anđela},
issn = {1091-6490},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = {7},
publisher = {Proceedings of the National Academy of Sciences},
title = {{Self-replication of Aβ42 aggregates occurs on small and isolated fibril sites}},
doi = {10.1073/pnas.2220075121},
volume = {121},
year = {2024},
}
@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 = {AbstractEndomembrane 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},
keywords = {Multidisciplinary},
publisher = {Springer Nature},
title = {{Stress granules plug and stabilize damaged endolysosomal membranes}},
doi = {10.1038/s41586-023-06726-w},
year = {2023},
}
@article{14844,
abstract = {Many cell functions require a concerted effort from multiple membrane proteins, for example, for signaling, cell division, and endocytosis. One contribution to their successful self-organization stems from the membrane deformations that these proteins induce. While the pairwise interaction potential of two membrane-deforming spheres has recently been measured, membrane-deformation-induced interactions have been predicted to be nonadditive, and hence their collective behavior cannot be deduced from this measurement. We here employ a colloidal model system consisting of adhesive spheres and giant unilamellar vesicles to test these predictions by measuring the interaction potential of the simplest case of three membrane-deforming, spherical particles. We quantify their interactions and arrangements and, for the first time, experimentally confirm and quantify the nonadditive nature of membrane-deformation-induced interactions. We furthermore conclude that there exist two favorable configurations on the membrane: (1) a linear and (2) a triangular arrangement of the three spheres. Using Monte Carlo simulations, we corroborate the experimentally observed energy minima and identify a lowering of the membrane deformation as the cause for the observed configurations. The high symmetry of the preferred arrangements for three particles suggests that arrangements of many membrane-deforming objects might follow simple rules.},
author = {Azadbakht, Ali and Meadowcroft, Billie and Majek, Juraj and Šarić, Anđela and Kraft, Daniela J.},
issn = {1542-0086},
journal = {Biophysical Journal},
publisher = {Elsevier},
title = {{Nonadditivity in interactions between three membrane-wrapped colloidal spheres}},
doi = {10.1016/j.bpj.2023.12.020},
year = {2023},
}
@article{13094,
abstract = {Endocytosis is a key cellular process involved in the uptake of nutrients, pathogens, or the therapy of diseases. Most studies have focused on spherical objects, whereas biologically relevant shapes can be highly anisotropic. In this letter, we use an experimental model system based on Giant Unilamellar Vesicles (GUVs) and dumbbell-shaped colloidal particles to mimic and investigate the first stage of the passive endocytic process: engulfment of an anisotropic object by the membrane. Our model has specific ligand–receptor interactions realized by mobile receptors on the vesicles and immobile ligands on the particles. Through a series of experiments, theory, and molecular dynamics simulations, we quantify the wrapping process of anisotropic dumbbells by GUVs and identify distinct stages of the wrapping pathway. We find that the strong curvature variation in the neck of the dumbbell as well as membrane tension are crucial in determining both the speed of wrapping and the final states.},
author = {Azadbakht, Ali and Meadowcroft, Billie and Varkevisser, Thijs and Šarić, Anđela and Kraft, Daniela J.},
issn = {1530-6992},
journal = {Nano Letters},
number = {10},
pages = {4267–4273},
publisher = {American Chemical Society},
title = {{Wrapping pathways of anisotropic dumbbell particles by Giant Unilamellar Vesicles}},
doi = {10.1021/acs.nanolett.3c00375},
volume = {23},
year = {2023},
}
@article{13237,
abstract = {The formation of amyloid fibrils is a general class of protein self-assembly behaviour, which is associated with both functional biology and the development of a number of disorders, such as Alzheimer and Parkinson diseases. In this Review, we discuss how general physical concepts from the study of phase transitions can be used to illuminate the fundamental mechanisms of amyloid self-assembly. We summarize progress in the efforts to describe the essential biophysical features of amyloid self-assembly as a nucleation-and-growth process and discuss how master equation approaches can reveal the key molecular pathways underlying this process, including the role of secondary nucleation. Additionally, we outline how non-classical aspects of aggregate formation involving oligomers or biomolecular condensates have emerged, inspiring developments in understanding, modelling and modulating complex protein assembly pathways. Finally, we consider how these concepts can be applied to kinetics-based drug discovery and therapeutic design to develop treatments for protein aggregation diseases.},
author = {Michaels, Thomas C.T. and Qian, Daoyuan and Šarić, Anđela and Vendruscolo, Michele and Linse, Sara and Knowles, Tuomas P.J.},
issn = {2522-5820},
journal = {Nature Reviews Physics},
pages = {379–397},
publisher = {Springer Nature},
title = {{Amyloid formation as a protein phase transition}},
doi = {10.1038/s42254-023-00598-9},
volume = {5},
year = {2023},
}
@article{13971,
abstract = {When in equilibrium, thermal forces agitate molecules, which then diffuse, collide and bind to form materials. However, the space of accessible structures in which micron-scale particles can be organized by thermal forces is limited, owing to the slow dynamics and metastable states. Active agents in a passive fluid generate forces and flows, forming a bath with active fluctuations. Two unanswered questions are whether those active agents can drive the assembly of passive components into unconventional states and which material properties they will exhibit. Here we show that passive, sticky beads immersed in a bath of swimming Escherichia coli bacteria aggregate into unconventional clusters and gels that are controlled by the activity of the bath. We observe a slow but persistent rotation of the aggregates that originates in the chirality of the E. coli flagella and directs aggregation into structures that are not accessible thermally. We elucidate the aggregation mechanism with a numerical model of spinning, sticky beads and reproduce quantitatively the experimental results. We show that internal activity controls the phase diagram and the structure of the aggregates. Overall, our results highlight the promising role of active baths in designing the structural and mechanical properties of materials with unconventional phases.},
author = {Grober, Daniel and Palaia, Ivan and Ucar, Mehmet C and Hannezo, Edouard B and Šarić, Anđela and Palacci, Jérémie A},
issn = {1745-2481},
journal = {Nature Physics},
pages = {1680--1688},
publisher = {Springer Nature},
title = {{Unconventional colloidal aggregation in chiral bacterial baths}},
doi = {10.1038/s41567-023-02136-x},
volume = {19},
year = {2023},
}
@article{12708,
abstract = {Self-organisation is the spontaneous emergence of spatio-temporal structures and patterns from the interaction of smaller individual units. Examples are found across many scales in very different systems and scientific disciplines, from physics, materials science and robotics to biology, geophysics and astronomy. Recent research has highlighted how self-organisation can be both mediated and controlled by confinement. Confinement is an action over a system that limits its units’ translational and rotational degrees of freedom, thus also influencing the system's phase space probability density; it can function as either a catalyst or inhibitor of self-organisation. Confinement can then become a means to actively steer the emergence or suppression of collective phenomena in space and time. Here, to provide a common framework and perspective for future research, we examine the role of confinement in the self-organisation of soft-matter systems and identify overarching scientific challenges that need to be addressed to harness its full scientific and technological potential in soft matter and related fields. By drawing analogies with other disciplines, this framework will accelerate a common deeper understanding of self-organisation and trigger the development of innovative strategies to steer it using confinement, with impact on, e.g., the design of smarter materials, tissue engineering for biomedicine and in guiding active matter.},
author = {Araújo, Nuno A.M. and Janssen, Liesbeth M.C. and Barois, Thomas and Boffetta, Guido and Cohen, Itai and Corbetta, Alessandro and Dauchot, Olivier and Dijkstra, Marjolein and Durham, William M. and Dussutour, Audrey and Garnier, Simon and Gelderblom, Hanneke and Golestanian, Ramin and Isa, Lucio and Koenderink, Gijsje H. and Löwen, Hartmut and Metzler, Ralf and Polin, Marco and Royall, C. Patrick and Šarić, Anđela and Sengupta, Anupam and Sykes, Cécile and Trianni, Vito and Tuval, Idan and Vogel, Nicolas and Yeomans, Julia M. and Zuriguel, Iker and Marin, Alvaro and Volpe, Giorgio},
issn = {1744-6848},
journal = {Soft Matter},
pages = {1695--1704},
publisher = {Royal Society of Chemistry},
title = {{Steering self-organisation through confinement}},
doi = {10.1039/d2sm01562e},
volume = {19},
year = {2023},
}
@article{12756,
abstract = {ESCRT-III family proteins form composite polymers that deform and cut membrane tubes in the context of a wide range of cell biological processes across the tree of life. In reconstituted systems, sequential changes in the composition of ESCRT-III polymers induced by the AAA–adenosine triphosphatase Vps4 have been shown to remodel membranes. However, it is not known how composite ESCRT-III polymers are organized and remodeled in space and time in a cellular context. Taking advantage of the relative simplicity of the ESCRT-III–dependent division system in Sulfolobus acidocaldarius, one of the closest experimentally tractable prokaryotic relatives of eukaryotes, we use super-resolution microscopy, electron microscopy, and computational modeling to show how CdvB/CdvB1/CdvB2 proteins form a precisely patterned composite ESCRT-III division ring, which undergoes stepwise Vps4-dependent disassembly and contracts to cut cells into two. These observations lead us to suggest sequential changes in a patterned composite polymer as a general mechanism of ESCRT-III–dependent membrane remodeling.},
author = {Hurtig, Fredrik and Burgers, Thomas C.Q. and Cezanne, Alice and Jiang, Xiuyun and Mol, Frank N. and Traparić, Jovan and Pulschen, Andre Arashiro and Nierhaus, Tim and Tarrason-Risa, Gabriel and Harker-Kirschneck, Lena and Löwe, Jan and Šarić, Anđela and Vlijm, Rifka and Baum, Buzz},
issn = {2375-2548},
journal = {Science Advances},
number = {11},
publisher = {American Association for the Advancement of Science},
title = {{The patterned assembly and stepwise Vps4-mediated disassembly of composite ESCRT-III polymers drives archaeal cell division}},
doi = {10.1126/sciadv.ade5224},
volume = {9},
year = {2023},
}
@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 = {Proceedings of the 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},
}
@article{10124,
abstract = {The transport of macromolecules and nanoscopic particles to a target cellular site is a crucial aspect in many physiological processes. This directional motion is generally controlled via active mechanical and chemical processes. Here we show, by means of molecular dynamics simulations and an analytical theory, that completely passive nanoparticles can exhibit directional motion when embedded in non-uniform mechanical environments. Specifically, we study the motion of a passive nanoparticle adhering to a mechanically non-uniform elastic membrane. We observe a non-monotonic affinity of the particle to the membrane as a function of the membrane’s rigidity, which results in the particle transport. This transport can be both up or down the rigidity gradient, depending on the absolute values of the rigidities that the gradient spans across. We conclude that rigidity gradients can be used to direct average motion of passive macromolecules and nanoparticles on deformable membranes, resulting in the preferential accumulation of the macromolecules in regions of certain mechanical properties.},
author = {Palaia, Ivan and Paraschiv, Alexandru and Debets, Vincent and Storm, Cornelis and Šarić, Anđela},
journal = {ACS Nano},
publisher = {American Chemical Society},
title = {{Durotaxis of passive nanoparticles on elastic membranes}},
doi = {10.1021/acsnano.1c02777 },
year = {2021},
}
@unpublished{10125,
abstract = {Living systems propagate by undergoing rounds of cell growth and division. Cell division is at heart a physical process that requires mechanical forces, usually exerted by protein assemblies. Here we developed the first physical model for the division of archaeal cells, which despite their structural simplicity share machinery and evolutionary origins with eukaryotes. We show how active geometry changes of elastic ESCRT-III filaments, coupled to filament disassembly, are sufficient to efficiently split the cell. We explore how the non-equilibrium processes that govern the filament behaviour impact the resulting cell division. We show how a quantitative comparison between our simulations and dynamic data for ESCRTIII-mediated division in Sulfolobus acidocaldarius, the closest archaeal relative to eukaryotic cells that can currently be cultured in the lab, and reveal the most likely physical mechanism behind its division.},
author = {Harker-Kirschneck, L. and Hafner, A. E. and Yao, T. and Pulschen, A. and Hurtig, F. and Vanhille-Campos, C. and Hryniuk, D. and Culley, S. and Henriques, R. and Baum, B. and Šarić, Anđela},
booktitle = {bioRxiv},
publisher = {Cold Spring Harbor Laboratory},
title = {{Physical mechanisms of ESCRT-III-driven cell division in archaea}},
doi = {10.1101/2021.03.23.436559},
year = {2021},
}
@article{10337,
abstract = {The T cell receptor (TCR) pathway receives, processes, and amplifies the signal from pathogenic antigens to the activation of T cells. Although major components in this pathway have been identified, the knowledge on how individual components cooperate to effectively transduce signals remains limited. Phase separation emerges as a biophysical principle in organizing signaling molecules into liquid-like condensates. Here, we report that phospholipase Cγ1 (PLCγ1) promotes phase separation of LAT, a key adaptor protein in the TCR pathway. PLCγ1 directly cross-links LAT through its two SH2 domains. PLCγ1 also protects LAT from dephosphorylation by the phosphatase CD45 and promotes LAT-dependent ERK activation and SLP76 phosphorylation. Intriguingly, a nonmonotonic effect of PLCγ1 on LAT clustering was discovered. Computer simulations, based on patchy particles, revealed how the cluster size is regulated by protein compositions. Together, these results define a critical function of PLCγ1 in promoting phase separation of the LAT complex and TCR signal transduction.},
author = {Zeng, Longhui and Palaia, Ivan and Šarić, Anđela and Su, Xiaolei},
issn = {1540-8140},
journal = {Journal of Cell Biology},
keywords = {cell biology},
number = {6},
publisher = {Rockefeller University Press},
title = {{PLCγ1 promotes phase separation of T cell signaling components}},
doi = {10.1083/jcb.202009154},
volume = {220},
year = {2021},
}
@article{10338,
abstract = {In the nuclear pore complex, intrinsically disordered proteins (FG Nups), along with their interactions with more globular proteins called nuclear transport receptors (NTRs), are vital to the selectivity of transport into and out of the cell nucleus. Although such interactions can be modeled at different levels of coarse graining, in vitro experimental data have been quantitatively described by minimal models that describe FG Nups as cohesive homogeneous polymers and NTRs as uniformly cohesive spheres, in which the heterogeneous effects have been smeared out. By definition, these minimal models do not account for the explicit heterogeneities in FG Nup sequences, essentially a string of cohesive and noncohesive polymer units, and at the NTR surface. Here, we develop computational and analytical models that do take into account such heterogeneity in a minimal fashion and compare them with experimental data on single-molecule interactions between FG Nups and NTRs. Overall, we find that the heterogeneous nature of FG Nups and NTRs does play a role in determining equilibrium binding properties but is of much greater significance when it comes to unbinding and binding kinetics. Using our models, we predict how binding equilibria and kinetics depend on the distribution of cohesive blocks in the FG Nup sequences and of the binding pockets at the NTR surface, with multivalency playing a key role. Finally, we observe that single-molecule binding kinetics has a rather minor influence on the diffusion of NTRs in polymer melts consisting of FG-Nup-like sequences.},
author = {Davis, Luke K. and Šarić, Anđela and Hoogenboom, Bart W. and Zilman, Anton},
issn = {0006-3495},
journal = {Biophysical Journal},
keywords = {biophysics},
number = {9},
pages = {1565--1577},
publisher = {Elsevier},
title = {{Physical modeling of multivalent interactions in the nuclear pore complex}},
doi = {10.1016/j.bpj.2021.01.039},
volume = {120},
year = {2021},
}
@article{10339,
abstract = {We study the effects of osmotic shocks on lipid vesicles via coarse-grained molecular dynamics simulations by explicitly considering the solute in the system. We find that depending on their nature (hypo- or hypertonic) such shocks can lead to bursting events or engulfing of external material into inner compartments, among other morphology transformations. We characterize the dynamics of these processes and observe a separation of time scales between the osmotic shock absorption and the shape relaxation. Our work consequently provides an insight into the dynamics of compartmentalization in vesicular systems as a result of osmotic shocks, which can be of interest in the context of early proto-cell development and proto-cell compartmentalisation.},
author = {Vanhille-Campos, Christian and Šarić, Anđela},
issn = {1744-6848},
journal = {Soft Matter},
keywords = {condensed matter physics, general chemistry},
number = {14},
pages = {3798--3806},
publisher = {Royal Society of Chemistry},
title = {{Modelling the dynamics of vesicle reshaping and scission under osmotic shocks}},
doi = {10.1039/d0sm02012e},
volume = {17},
year = {2021},
}
@article{10340,
abstract = {The cell membrane is an inhomogeneous system composed of phospholipids, sterols, carbohydrates, and proteins that can be directly attached to underlying cytoskeleton. The protein linkers between the membrane and the cytoskeleton are believed to have a profound effect on the mechanical properties of the cell membrane and its ability to reshape. Here, we investigate the role of membrane-cortex linkers on the extrusion of membrane tubes using computer simulations and experiments. In simulations, we find that the force for tube extrusion has a nonlinear dependence on the density of membrane-cortex attachments: at a range of low and intermediate linker densities, the force is not significantly influenced by the presence of the membrane-cortex attachments and resembles that of the bare membrane. For large concentrations of linkers, however, the force substantially increases compared with the bare membrane. In both cases, the linkers provided membrane tubes with increased stability against coalescence. We then pulled tubes from HEK cells using optical tweezers for varying expression levels of the membrane-cortex attachment protein Ezrin. In line with simulations, we observed that overexpression of Ezrin led to an increased extrusion force, while Ezrin depletion had a negligible effect on the force. Our results shed light on the importance of local protein rearrangements for membrane reshaping at nanoscopic scales.},
author = {Paraschiv, Alexandru and Lagny, Thibaut J. and Campos, Christian Vanhille and Coudrier, Evelyne and Bassereau, Patricia and Šarić, Anđela},
issn = {0006-3495},
journal = {Biophysical Journal},
keywords = {biophysics},
number = {4},
pages = {598--606},
publisher = {Cell Press},
title = {{Influence of membrane-cortex linkers on the extrusion of membrane tubes}},
doi = {10.1016/j.bpj.2020.12.028},
volume = {120},
year = {2021},
}