@article{21369, abstract = {Formation of new amyloid fibrils and oligomers from monomeric protein on the surfaces of existing fibrils is an important driver of many disorders such as Alzheimer’s and Parkinson’s diseases. The structural basis of this secondary nucleation process, however, is poorly understood. Here, we ask whether secondary nucleation sites are found predominantly at rare growth defects: irregularities in the fibril core structure incorporated during their original assembly. We first demonstrate using the specific inhibitor of secondary nucleation, Brichos, that secondary nucleation sites on Alzheimer’s disease-associated fibrils composed of Aβ40 and Aβ42 peptides are rare compared to the number of protein molecules they contain. We then grow Aβ40 fibrils under conditions designed to eliminate most growth defects while leaving the regular fibril morphology unchanged, and confirm the latter using cryo-electron microscopy. We measure both the ability of these annealed fibrils to promote secondary nucleation and the stoichiometry of their secondary nucleation sites, finding that both are greatly reduced as predicted. Re-analysis of published data for other proteins suggests that fibril growth defects may also drive secondary nucleation generally across most amyloids. These findings could unlock structure-based drug design of therapeutics that aim to halt amyloid disorders by inhibiting secondary nucleation sites.}, author = {Hu, Jing and Scheidt, Tom and Thacker, Dev and Axell, Emil and Stemme, Elin and Łapińska, Urszula and Wennmalm, Stefan and Meisl, Georg and Curk, Samo and Andreasen, Maria and Vendruscolo, Michele and Arosio, Paolo and Šarić, Anđela and Schmit, Jeremy D. and Knowles, Tuomas P.J. and Sparr, Emma and Linse, Sara and Michaels, Thomas C.T. and Dear, Alexander J.}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Structural defects in amyloid-β fibrils drive secondary nucleation}}, doi = {10.1038/s41467-026-69377-1}, volume = {17}, year = {2026}, } @article{21764, abstract = {Colloidal fluids can exhibit complex phase behavior and determining phase diagrams via experiments or computer simulations can be laborious. We demonstrate that the dispersion relation ω(k), obtained from dynamical density functional theory for the uniform density system, is a highly versatile tool for predicting where in the phase diagram complex crystals form. The sign of ω(k) determines whether density modes with wave number k grow or decay over time. We demonstrate the predictive power by investigating the complex phase behavior of particles interacting via core-shoulder pair potentials. With complementary Monte Carlo simulations, we show that regions of the phase diagram where ωðkÞ has one or several unstable (growing) wave numbers are also where crystalline phases occur. Going further, by tuning these unstable wave numbers via the interaction-potential and state-point parameters, we design systems with quasicrystals in the phase diagram. We identify a system with a certain shoulder range exhibiting at least ten different phases. Our general approach accelerates considerably the mapping of complex phase diagrams, crucial for the design of new materials.}, author = {Wassermair, Michael and Kahl, Gerhard and Roth, Roland and Archer, Andrew J.}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {14}, publisher = {American Physical Society}, title = {{Navigating complex phase diagrams in soft matter systems}}, doi = {10.1103/nbvt-fgjy}, volume = {136}, year = {2026}, } @article{21761, abstract = {Neural tube closure is a critical morphogenetic process in vertebrate development, and failure to close cranial regions such as the hindbrain neuropore (HNP) leads to severe congenital malformations. While mechanical forces such as actomyosin purse-string contraction and directional cell crawling have been implicated in driving HNP closure, how these forces organize local cell shape and motion to produce large-scale tissue remodeling remains poorly understood. Using live and fixed imaging of mouse embryos combined with cell-based biophysical modeling, we show that these force-generating mechanisms are insufficient to explain the reproducible patterns of cell elongation and nematic alignment observed at the HNP border. Instead, we show that local anisotropic stress and cytoskeletal organization are required to generate these patterns and promote midline cell motion. Our model captures key features of cell shape dynamics and emergent nematic order, which we confirm experimentally, including the alignment of actin fibers with cell shape and enhanced midline cell speed. Comparative analysis with chick embryos, which lack supracellular purse strings, supports a conserved link between tension generation and cellular patterning. These findings establish a physical framework connecting force generation, cell shape anisotropy, and tissue morphodynamics during epithelial gap closure.}, author = {Perez Verdugo, Fernanda L and Maniou, Eirini and Galea, Gabriel L. and Banerjee, Shiladitya}, issn = {1879-0445}, journal = {Current Biology}, number = {8}, pages = {1903--1917.e5}, publisher = {Elsevier}, title = {{Mechanosensitive feedback organizes cell shape and motion during hindbrain neuropore morphogenesis}}, doi = {10.1016/j.cub.2026.02.068}, volume = {36}, year = {2026}, } @article{21748, abstract = {Cells are defined by lipid membranes that differ in their structure across the tree of life. While the membranes of most bacteria and eukaryotes consist of single-headed bilayer lipids, the membranes of archaea are composed of mixtures of single-headed bilayer lipids and double-headed bolalipids. Archaeal bolalipids can adopt straight or u-shaped conformations, enabling them—together with bilayer lipids—to control whether membranes form bilayer or monolayer structures. Yet, the physical principles governing archaeal membranes remain largely unexplored, especially how membrane structure couples to externally imposed curvature during membrane remodeling. Here, we perform coarse-grained molecular dynamics simulations of toroidal vesicles to systematically probe the effects of all relevant combinations of mean and Gaussian curvatures on shape stability and lipid organization. We find that soft bilayer membranes can sustain all curvatures induced, whereas rigid bolalipid monolayer membranes either transition to different vesicle shapes or rupture. Bilayer-mimicking u-shaped bolalipids and bilayer lipids are spatially accumulated in regions of high mean membrane curvature independent of Gaussian curvature. Our work identifies curvature–composition coupling as a physical signature of archaeal membrane remodeling.}, author = {Frey, Felix F and Santana de Freitas Amaral, Miguel and Šarić, Anđela}, issn = {1089-7690}, journal = {Journal of Chemical Physics}, number = {14}, publisher = {AIP Publishing}, title = {{Cracking donuts and sorting lipids: Geometry controls archaeal membrane stability and lipid organization}}, doi = {10.1063/5.0325170}, volume = {164}, year = {2026}, } @misc{21800, abstract = {LAMMPS input scripts to simulate toroidal vesicles composed of pure bolalipid membranes and archaeal mixture membranes for the following publication: "Cracking donuts and sorting lipids: geometry controls archaeal membrane stability and lipid organization" by Felix Frey, Miguel Amaral, and Andela Saric.}, author = {Frey, Felix F and Santana de Freitas Amaral, Miguel and Šarić, Anđela}, publisher = {Zenodo}, title = {{Cracking donuts and sorting lipids: Geometry controls archaeal membrane stability and lipid organization}}, doi = {10.5281/ZENODO.18772086}, year = {2026}, } @article{21749, abstract = {The collagen triple helix assembles hierarchically into bundled oligomers, solvated networks, and fibers. Synthetic peptide assemblies, driven by supramolecular interactions, can form single triple helices through intrahelical amino acid pairs; however, the principles guiding interhelical associations into higher-order structures remain unclear. Here, we incorporate cation−π and electrostatic charge pairs to probe interhelical interactions and elucidate the mechanisms driving triple helix assembly into fibrils, nanotubes, and nanosheets. Introducing cation−π pairs into a fibrillating collagen mimetic resulted in D-periodic fibrils with pH-sensitive gelation. By alternating the presentation of electrostatic and cation−π pairs, the assembly of another D-periodic fibril featuring inner and outer triple-helical layers was resolved by cryo electron microscopy to a resolution of 8 Å. At physiological pH, antiparallel association of these triple helices leads to the formation of nanotubes. The packing behavior of triple helices correlates with the interhelical interactions, where parallel associations favor fibril formation and antiparallel interactions drive nanotube and nanosheet assembly. These self-assembling triple-helical peptides demonstrate how packing of higher-order structures can be tailored with supramolecular interactions and establish the relationship of different hierarchical collagen-mimetic assemblies as pH-dependent.}, author = {Cole, Carson C. and Kreutzberger, Mark A.B. and Klein, Kevin and Cahue, Kiana A. and Pogostin, Brett H. and Farsheed, Adam C. and Swain, Joseph W.R. and Bui, Thi H. and Dey, Arghadip and Makhoul, Jonathan T. and Dubackic, Marija and Pal, Antara and Olsson, Ulf and Šarić, Anđela and Egelman, Edward H. and Hartgerink, Jeffrey D.}, issn = {1526-4602}, journal = {Biomacromolecules}, number = {4}, pages = {2956--2965}, publisher = {American Chemical Society}, title = {{Supramolecular assembly of collagen-mimetic eptide D-periodic fibrils and nanoassemblies}}, doi = {10.1021/acs.biomac.6c00345}, volume = {27}, year = {2026}, } @article{19846, abstract = {The Ca2+-release-activated Ca2+ (CRAC) channel Orai1 is activated by interaction with the Ca2+ sensor Stromal Interaction Molecule 1 (STIM1). Owing to the lack of structurally resolved Orai1/STIM1 complexes, the impact of their coupling on individual Orai1 transmembrane domain (TM) movements is unclear. This study investigates STIM1-independent and STIM1-dependent Orai1-TM dynamics using photocrosslinking unnatural amino acids (UAAs) at each individual TM position. We primarily identify CRAC-channel-like currents directly after UAA incorporation or additional UV-light irradiation at TM3 sites that interface with non-pore-lining TMs. Using UAAs combined with conventional site-directed mutagenesis and molecular dynamics simulations, we discover that pore opening involves a widening of interfaces formed by TM3 with non-pore-lining TMs. Orai1 mutants with a UAA in TM3 exhibit weaker STIM1-induced activation after UV exposure, possibly caused by a restricted widening of non-pore-lining TM interfaces. We demonstrate that photocrosslinking UAAs are excellent tools for improving our understanding of key determinants and ion channel dynamics modulating pore opening.}, author = {Najjar, Hadil and Weiß, Sarah and Horvath, Ferdinand and Hopl, Valentina and Tiffner, Adéla and Höbarth, Lorenz and Söllner, Julia and Fröhlich, Maximilian and Prantl, Magdalena and Müller, Nora and Nazarenko, Yuliia and Harant, Selina and Weissenböck, Lukas and Grabmayr, Herwig and Sallinger, Matthias and Maltan, Lena and Echefu, Linda V. and Radiskovic, Tamara and Leopold, Melanie and Lindinger, Sonja and Humer, Christina and Höglinger, Carmen and Krobath, Heinrich and Renger, Thomas and Derler, Isabella}, issn = {2666-3864}, journal = {Cell Reports Physical Science}, number = {6}, publisher = {Elsevier}, title = {{STIM1-induced widening of non-pore-lining TM interfaces is crucial for Orai1 pore opening}}, doi = {10.1016/j.xcrp.2025.102623}, volume = {6}, year = {2025}, } @article{20318, abstract = {Lipid membranes and membrane deformations are a long-standing area of research in soft matter and biophysics. Computer simulations have complemented analytical and experimental approaches as one of the pillars in the field. However, setting up and using membrane simulations can come with barriers due to the multidisciplinary effort involved and the vast choice of existing simulations models. In this review, we introduce the non-expert reader to coarse-grained membrane simulations at the mesoscale. Firstly, we give a concise overview of the modelling approaches to study fluid membranes, together with guidance to more specialized references. Secondly, we provide a conceptual guide on how to develop mesoscale membrane simulations. Lastly, we construct a hands-on tutorial on how to apply mesoscale membrane simulations, by providing a pedagogical examination of membrane tether pulling, shape and mechanics of membrane tubes, and membrane fluctuations with three different membrane models, and discussing them in terms of their scope and how resource-intensive they are. To ease the reader's venture into the field, we provide a repository with ready-to-run tutorials.}, author = {Muñoz Basagoiti, Maitane and Frey, Felix F and Meadowcroft, Billie and Santana de Freitas Amaral, Miguel and Prada, Adam and Šarić, Anđela}, issn = {1744-6848}, journal = {Soft Matter}, number = {40}, pages = {7736--7756}, publisher = {Royal Society of Chemistry}, title = {{A tutorial for mesoscale computer simulations of lipid membranes: Tether pulling, tubulation and fluctuations}}, doi = {10.1039/d5sm00148j}, volume = {21}, year = {2025}, } @article{20477, abstract = {An electric double-layer capacitor (EDLC) stores energy by modulating the spatial distribution of ions in the electrolytic solution that it contains. We determine the mean-field timescales for planar EDLC relaxation to equilibrium after a potential difference is applied. We tackle first the fully symmetric case, where positive and negative ionic species have the same valence and diffusivity, and then the general, more complex, asymmetric case. Depending on the applied voltage and salt concentration, different regimes appear, revealing a remarkably rich phenomenology relevant for nanocapacitors.}, author = {Palaia, Ivan and Asta, Adelchi J. and Dutta, Megh and Warren, Patrick B. and Rotenberg, Benjamin and Trizac, Emmanuel}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {14}, publisher = {American Physical Society}, title = {{Charging dynamics of electric double-layer nanocapacitors in mean field}}, doi = {10.1103/72b9-c8cq}, volume = {135}, year = {2025}, } @article{20483, abstract = {A parallel plate capacitor containing an electrolytic solution is the simplest model of a supercapacitor or electric double-layer capacitor. Using both analytical and numerical techniques, we solve the Poisson-Nernst-Planck equations for such a system, describing the mean-field charging dynamics of the capacitor, when a constant potential difference is abruptly applied to its plates. Working at constant total number of ions, we focus on the physical processes involved in the relaxation and, whenever possible, give its functional shape and exact time constants. We first review and study the case of a symmetric binary electrolyte, where we assume the two ionic species to have the same charges and diffusivities. We then relax these assumptions and present results for a generic strong (i.e fully dissociated) binary electrolyte. At low electrolyte concentration, the relaxation is simple to understand, as the dynamics of positive and negative ions appear decoupled. At higher electrolyte concentration, we distinguish several regimes. In the linear regime (low voltages), relaxation is multiexponential, it starts by the buildup of the equilibrium charge profile and continues with neutral mass diffusion, and the relevant timescales feature both the average and the Nernst-Hartley diffusion coefficients. In the purely nonlinear regime (intermediate voltages), the initial relaxation is slowed down exponentially due to increased capacitance, while bulk effects become more and more evident. In the fully nonlinear regime (high voltages), the dynamics of charge and mass are completely entangled and, asymptotically, the relaxation is linear in time. We finally discuss nonideal behavior in real capacitors and provide conditions for which mean-field is expected to hold.}, author = {Palaia, Ivan and Asta, Adelchi J. and Dutta, Megh and Warren, Patrick B. and Rotenberg, Benjamin and Trizac, Emmanuel}, issn = {2470-0053}, journal = {Physical Review E}, number = {3}, publisher = {American Physical Society}, title = {{Poisson-Nernst-Planck charging dynamics of an electric double-layer capacitor: Symmetric and asymmetric binary electrolytes}}, doi = {10.1103/p4dg-snqf}, volume = {112}, year = {2025}, } @article{20530, abstract = {Cells must coordinate DNA segregation with cytokinesis to ensure that each daughter cell inherits a complete genome. Here, we explore how DNA segregation and division are mechanistically coupled in archaeal relatives of eukaryotes, which lack Cyclin-dependent kinase (CDK)/Cyclins. Using live cell imaging, we first describe the series of sequential changes in DNA organization that accompany cell division in Sulfolobus, which computational modeling shows likely aid genome segregation. Through a perturbation analysis we identify a regulatory checkpoint which ensures that the compaction of the genome into two spatially segregated nucleoids only occurs once cells have assembled a division ring—which also defines the axis of DNA segregation. Finally, we show that DNA compaction and segregation depend, in part, on a ParA homologue, SegA, and its partner SegB, whose absence leads to bridging DNA. Taken together, these data show how regulatory checkpoints like those operating in eukaryotes aid high-fidelity division in an archaeon.}, author = {Parham, Joe and Sorichetti, Valerio and Cezanne, Alice and Foo, Sherman and Kuo, Yin Wei and Hoogenberg, Baukje and Radoux-Mergault, Arthur and Mawdesley, Eloise and Gatward, Lydia Daniels and Boulanger, Jerome and Schulze, Ulrike and Šarić, Anđela and Baum, Buzz}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {42}, pages = {e2513939122}, publisher = {National Academy of Sciences}, title = {{Temporal and spatial coordination of DNA segregation and cell division in an archaeon}}, doi = {10.1073/pnas.2513939122}, volume = {122}, year = {2025}, } @article{18820, abstract = {Feature selection is essential in the analysis of molecular systems and many other fields, but several uncertainties remain: What is the optimal number of features for a simplified, interpretable model that retains essential information? How should features with different units be aligned, and how should their relative importance be weighted? Here, we introduce the Differentiable Information Imbalance (DII), an automated method to rank information content between sets of features. Using distances in a ground truth feature space, DII identifies a low-dimensional subset of features that best preserves these relationships. Each feature is scaled by a weight, which is optimized by minimizing the DII through gradient descent. This allows simultaneously performing unit alignment and relative importance scaling, while preserving interpretability. DII can also produce sparse solutions and determine the optimal size of the reduced feature space. We demonstrate the usefulness of this approach on two benchmark molecular problems: (1) identifying collective variables that describe conformations of a biomolecule, and (2) selecting features for training a machine-learning force field. These results show the potential of DII in addressing feature selection challenges and optimizing dimensionality in various applications. The method is available in the Python library DADApy.}, author = {Wild, Romina and Wodaczek, Felix and Del Tatto, Vittorio and Cheng, Bingqing and Laio, Alessandro}, issn = {2041-1723}, journal = {Nature Communications}, publisher = {Springer Nature}, title = {{Automatic feature selection and weighting in molecular systems using Differentiable Information Imbalance}}, doi = {10.1038/s41467-024-55449-7}, volume = {16}, year = {2025}, } @article{21235, abstract = {The condensation of charged polymers is an important driver for the formation of biomolecular condensates. Recent experiments suggest that this mechanism also controls the clustering of eukaryotic chromosomes during the late stages of cell division. In this process, interchromosome attraction is driven by the condensation of cytoplasmic RNA and Ki-67, a charged intrinsically disordered protein that coats the chromosomes as a brush. Attraction between chromosomes has been shown to be specifically promoted by a localized charged patch on Ki-67, although the physical mechanism remains unclear. To elucidate this process, we combine coarse-grained simulations and analytical theory to study the RNA-mediated interaction between charged polymer brushes on the chromosome surfaces. We show that the charged patch on Ki-67 leads to interchromosome attraction via RNA bridging between the two brushes, whereby the RNA preferentially interacts with the charged patches, leading to stable, long-range forces. By contrast, if the brush is uniformly charged, bridging is basically absent due to complete adsorption of RNA onto the brush. Moreover, the RNA dynamics becomes caged in presence of the charged patch while remaining diffusive with uniform charge. Our work sheds light on the physical origin of chromosome clustering, while also suggesting a general mechanism for cells to tune work production by biomolecular condensates via different charge distributions.}, author = {Sorichetti, Valerio and Robin, Paul and Palaia, Ivan and Hernandez-Armendariz, Alberto and Cuylen-Haering, Sara and Šarić, Anđela}, issn = {2835-8279}, journal = {PRX Life}, number = {3}, publisher = {American Physical Society}, title = {{Charge distribution of the coating brush drives interchromosome attraction}}, doi = {10.1103/41fd-r847}, volume = {3}, year = {2025}, } @article{21251, abstract = {Cellular membranes differ across the tree of life. In most bacteria and eukaryotes, single-headed lipids self-assemble into flexible bilayer membranes. By contrast, thermophilic archaea tend to possess bilayer lipids together with double-headed, monolayer spanning bolalipids, which are thought to enable cells to survive in harsh environments. Here, using a minimal computational model for bolalipid membranes, we explore the trade-offs at play when forming membranes. We find that flexible bolalipids form membranes that resemble bilayer membranes because they are able to assume a U-shaped conformation. Conversely, rigid bolalipids, which resemble the bolalipids with cyclic groups found in thermophilic archaea, take on a straight conformation and form membranes that are stiff and prone to pore formation when they undergo changes in shape. Strikingly, however, the inclusion of small amounts of bilayer lipids in a bolalipid membrane is enough to achieve fluid bolalipid membranes that are both stable and flexible, resolving this trade-off. Our study suggests a mechanism by which archaea can tune the material properties of their membranes as and when required to enable them to survive in harsh environments and to undergo essential membrane remodelling events like cell division.}, author = {Santana de Freitas Amaral, Miguel and Frey, Felix F and Jiang, Xiuyun and Baum, Buzz and Šarić, Anđela}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Balancing stability and flexibility when reshaping archaeal membranes}}, doi = {10.7554/elife.105432}, volume = {14}, year = {2025}, } @article{21256, abstract = {Collagen IV is one of the main components of the basement membrane, a layer of material that lines the majority of tissues in multicellular organisms. Collagen IV molecules assemble into networks, providing stiffness and elasticity to tissues and informing cell and organ shape, especially during development. In this work, we develop two coarse-grained models for collagen IV molecules that retain biochemical bond specificity and coarse grain at different length scales. Through molecular-dynamics simulations, we test the assembly and mechanics of the resulting networks and measure their response to strain in terms of stress, microscopic alignment, and bond dynamics. Within the basement membrane, collagen IV networks rearrange by molecule turnover, which affects tissue organization and can be linked with enzyme activity. Here we explore network rearrangements via bond remodeling, the process of breaking and remaking of bonds between network molecules. We then investigate the effects of active (enzymatic) bond remodeling. We find that this nonequilibrium remodeling allows a network to keep its integrity under strain, while relaxing fully over a variety of timescales, a dynamic response that is unavailable to networks undergoing equilibrium remodeling.}, author = {Meadowcroft, Billie and Sorichetti, Valerio and Ratajczyk, Eryk and Perez Verdugo, Fernanda L and Khalilgharibi, Nargess and Mao, Yanlan and Palaia, Ivan and Šarić, Anđela}, issn = {2835-8279}, journal = {PRX Life}, publisher = {American Physical Society}, title = {{Nonequilibrium remodeling of collagen IV networks in Silico}}, doi = {10.1103/gdd5-rnh7}, volume = {3}, year = {2025}, } @unpublished{21427, abstract = {While tumor malignancy has been extensively studied under the prism of genetic and epigenetic heterogeneity, tumor cell states also critically depend on reciprocal interactions with the microenvironment. This raises the hitherto untested possibility that heterogeneity of the untransformed tumor stroma can actively fuel malignant progression. As biological heterogeneity is inherently difficult to control, we adopted a reductionist approach and let tumor cells invade micro-engineered environments harboring obstacles with precision-controlled geometry. We find that not only the presence of obstacles, but more surprisingly their spatial disorder, causes a drastic shift from a collective to a single-cell mode of invasion – comparable in strength to cadherin loss. Combining live-imaging and perturbation experiments with minimal biophysical modeling, we demonstrate that cell detachments result both from local geometrical constraints and a global integration of spatial disorder over time. We show that different types of microenvironments map onto different universality classes of invasion dynamics - homogeneous substrates follow Kardar–Parisi–Zhang (KPZ) scaling, while disordered ones exhibit exponents consistent with KPZ with quenched disorder (KPZq). Our findings highlight generic physical principles for how the mode of cancer cell invasion depends on environmental heterogeneity, with potential implications to understand tumor evolution in vivo.}, author = {Dunajova, Zuzana and Tasciyan, Saren and Majek, Juraj and Merrin, Jack and Sahai, Erik and Sixt, Michael K and Hannezo, Edouard B}, publisher = {bioRxiv}, title = {{Substrate heterogeneity promotes cancer cell dissemination through interface roughening}}, doi = {10.1101/2025.05.20.655037}, year = {2025}, } @article{18072, abstract = {The individualization of chromosomes during early mitosis and their clustering upon exit from cell division are two key transitions that ensure efficient segregation of eukaryotic chromosomes. Both processes are regulated by the surfactant-like protein Ki-67, but how Ki-67 achieves these diametric functions has remained unknown. Here, we report that Ki-67 radically switches from a chromosome repellent to a chromosome attractant during anaphase in human cells. We show that Ki-67 dephosphorylation during mitotic exit and the simultaneous exposure of a conserved basic patch induce the RNA-dependent formation of a liquid-like condensed phase on the chromosome surface. Experiments and coarse-grained simulations support a model in which the coalescence of chromosome surfaces, driven by co-condensation of Ki-67 and RNA, promotes clustering of chromosomes. Our study reveals how the switch of Ki-67 from a surfactant to a liquid-like condensed phase can generate mechanical forces during genome segregation that are required for re-establishing nuclear-cytoplasmic compartmentalization after mitosis.}, author = {Hernandez-Armendariz, Alberto and Sorichetti, Valerio and Hayashi, Yuki and Koskova, Zuzana and Brunner, Andreas and Ellenberg, Jan and Šarić, Anđela and Cuylen-Haering, Sara}, issn = {1097-4164}, journal = {Molecular Cell}, number = {17}, pages = {P3254--3270.E9}, publisher = {Cell Press}, title = {{A liquid-like coat mediates chromosome clustering during mitotic exit}}, doi = {10.1016/j.molcel.2024.07.022}, volume = {84}, year = {2024}, } @article{18526, abstract = {Multivesicular endosomes (MVEs) sequester membrane proteins destined for degradation within intralumenal vesicles (ILVs), a process mediated by the membrane-remodeling action of Endosomal Sorting Complex Required for Transport (ESCRT) proteins. In Arabidopsis, endosomal membrane constriction and scission are uncoupled, resulting in the formation of extensive concatenated ILV networks and enhancing cargo sequestration efficiency. Here, we used a combination of electron tomography, computer simulations, and mathematical modeling to address the questions of when concatenated ILV networks evolved in plants and what drives their formation. Through morphometric analyses of tomographic reconstructions of endosomes across yeast, algae, and various land plants, we have found that ILV concatenation is widespread within plant species, but only prevalent in seed plants, especially in flowering plants. Multiple budding sites that require the formation of pores in the limiting membrane were only identified in hornworts and seed plants, suggesting that this mechanism has evolved independently in both plant lineages. To identify the conditions under which these multiple budding sites can arise, we used particle-based molecular dynamics simulations and found that changes in ESCRT filament properties, such as filament curvature and membrane binding energy, can generate the membrane shapes observed in multiple budding sites. To understand the relationship between membrane budding activity and ILV network topology, we performed computational simulations and identified a set of membrane remodeling parameters that can recapitulate our tomographic datasets.}, author = {Weiner, Ethan and Berryman, Elizabeth and Frey, Felix F and Solís, Ariadna González and Leier, André and Lago, Tatiana Marquez and Šarić, Anđela and Otegui, Marisa S.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {44}, publisher = {National Academy of Sciences}, title = {{Endosomal membrane budding patterns in plants}}, doi = {10.1073/pnas.2409407121}, volume = {121}, year = {2024}, } @article{18704, abstract = {Clathrin-mediated endocytosis is the main pathway used by eukaryotic cells to take up extracellular material, but the dominant physical mechanisms driving this process are still elusive. Recently, several high-resolution imaging techniques have been used on different cell lines to measure the geometrical properties of clathrin-coated pits over their whole lifetime. Here, we first show that the combination of all datasets with the recently introduced cooperative curvature model defines a consensus pathway, which is characterized by a flat-to-curved transition at finite area, followed by linear growth and subsequent saturation of curvature. We then apply an energetic model for the composite of the plasma membrane and clathrin coat to this consensus pathway to show that the dominant mechanism for invagination could be coat stiffening, which might originate from cooperative interactions between the different clathrin molecules and progressively drives the system toward its intrinsic curvature. Our theory predicts that two length scales determine the invagination pathway, namely the patch size at which the flat-to-curved transition occurs and the final pit radius.}, author = {Frey, Felix F and Schwarz, Ulrich S.}, issn = {2470-0053}, journal = {Physical Review E}, number = {6}, publisher = {American Physical Society}, title = {{Coat stiffening can explain invagination of clathrin-coated membranes}}, doi = {10.1103/PhysRevE.110.064403}, volume = {110}, year = {2024}, } @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}, number = {3}, pages = {307--316}, publisher = {Elsevier}, title = {{Nonadditivity in interactions between three membrane-wrapped colloidal spheres}}, doi = {10.1016/j.bpj.2023.12.020}, volume = {123}, year = {2024}, }