@article{9060, abstract = {Molecular motors are essential to the living, generating fluctuations that boost transport and assist assembly. Active colloids, that consume energy to move, hold similar potential for man-made materials controlled by forces generated from within. Yet, their use as a powerhouse in materials science lacks. Here we show a massive acceleration of the annealing of a monolayer of passive beads by moderate addition of self-propelled microparticles. We rationalize our observations with a model of collisions that drive active fluctuations and activate the annealing. The experiment is quantitatively compared with Brownian dynamic simulations that further unveil a dynamical transition in the mechanism of annealing. Active dopants travel uniformly in the system or co-localize at the grain boundaries as a result of the persistence of their motion. Our findings uncover the potential of internal activity to control materials and lay the groundwork for the rise of materials science beyond equilibrium.}, author = {Ramananarivo, Sophie and Ducrot, Etienne and Palacci, Jérémie A}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology, General Physics and Astronomy, General Chemistry}, number = {1}, publisher = {Springer Nature}, title = {{Activity-controlled annealing of colloidal monolayers}}, doi = {10.1038/s41467-019-11362-y}, volume = {10}, year = {2019}, } @article{13374, abstract = {Confining molecules to volumes only slightly larger than the molecules themselves can profoundly alter their properties. Molecular switches—entities that can be toggled between two or more forms upon exposure to an external stimulus—often require conformational freedom to isomerize. Therefore, placing these switches in confined spaces can render them non-operational. To preserve the switchability of these species under confinement, we work with a water-soluble coordination cage that is flexible enough to adapt its shape to the conformation of the encapsulated guest. We show that owing to its flexibility, the cage is not only capable of accommodating—and solubilizing in water—several light-responsive spiropyran-based molecular switches, but, more importantly, it also provides an environment suitable for the efficient, reversible photoisomerization of the bound guests. Our findings pave the way towards studying various molecular switching processes in confined environments.}, author = {Samanta, Dipak and Galaktionova, Daria and Gemen, Julius and Shimon, Linda J. W. and Diskin-Posner, Yael and Avram, Liat and Král, Petr and Klajn, Rafal}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{Reversible chromism of spiropyran in the cavity of a flexible coordination cage}}, doi = {10.1038/s41467-017-02715-6}, volume = {9}, year = {2018}, } @article{14003, abstract = {Molecular chirality plays an essential role in most biochemical processes. The observation and quantification of chirality-sensitive signals, however, remains extremely challenging, especially on ultrafast timescales and in dilute media. Here, we describe the experimental realization of an all-optical and ultrafast scheme for detecting chiral dynamics in molecules. This technique is based on high-harmonic generation by a combination of two-color counterrotating femtosecond laser pulses with polarization states tunable from linear to circular. We demonstrate two different implementations of chiral-sensitive high-harmonic spectroscopy on an ensemble of randomly oriented methyloxirane molecules in the gas phase. Using two elliptically polarized fields, we observe that the ellipticities maximizing the harmonic signal reach up to 4.4 ± 0.2 % (at 17.6 eV). Using two circularly polarized fields, we observe circular dichroisms ranging up to 13 ± 6 % (28.3–33.1 eV). Our theoretical analysis confirms that the observed chiral response originates from subfemtosecond electron dynamics driven by the magnetic component of the driving laser field. This assignment is supported by the experimental observation of a strong intensity dependence of the chiral effects and its agreement with theory. We moreover report and explain a pronounced variation of the signal strength and dichroism with the driving-field ellipticities and harmonic orders. Finally, we demonstrate the sensitivity of the experimental observables to the shape of the electron hole. This technique for chiral discrimination will yield femtosecond temporal resolution when integrated in a pump-probe scheme and subfemtosecond resolution on chiral charge migration in a self-probing scheme.}, author = {Baykusheva, Denitsa Rangelova and Wörner, Hans Jakob}, issn = {2160-3308}, journal = {Physical Review X}, keywords = {General Physics and Astronomy}, number = {3}, publisher = {American Physical Society}, title = {{Chiral discrimination through bielliptical high-harmonic spectroscopy}}, doi = {10.1103/physrevx.8.031060}, volume = {8}, year = {2018}, } @article{14284, abstract = {Pore-forming toxins (PFT) are virulence factors that transform from soluble to membrane-bound states. The Yersinia YaxAB system represents a family of binary α-PFTs with orthologues in human, insect, and plant pathogens, with unknown structures. YaxAB was shown to be cytotoxic and likely involved in pathogenesis, though the molecular basis for its two-component lytic mechanism remains elusive. Here, we present crystal structures of YaxA and YaxB, together with a cryo-electron microscopy map of the YaxAB complex. Our structures reveal a pore predominantly composed of decamers of YaxA–YaxB heterodimers. Both subunits bear membrane-active moieties, but only YaxA is capable of binding to membranes by itself. YaxB can subsequently be recruited to membrane-associated YaxA and induced to present its lytic transmembrane helices. Pore formation can progress by further oligomerization of YaxA–YaxB dimers. Our results allow for a comparison between pore assemblies belonging to the wider ClyA-like family of α-PFTs, highlighting diverse pore architectures.}, author = {Bräuning, Bastian and Bertosin, Eva and Praetorius, Florian M and Ihling, Christian and Schatt, Alexandra and Adler, Agnes and Richter, Klaus and Sinz, Andrea and Dietz, Hendrik and Groll, Michael}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{Structure and mechanism of the two-component α-helical pore-forming toxin YaxAB}}, doi = {10.1038/s41467-018-04139-2}, volume = {9}, year = {2018}, } @article{15232, abstract = {In this paper we describe the potential of the enhanced X-ray Timing and Polarimetry (eXTP) mission for studies related to accretion flows in the strong field gravity regime around both stellar-mass and supermassive black-holes. eXTP has the unique capability of using advanced “spectral-timing-polarimetry” techniques to analyze the rapid variations with three orthogonal diagnostics of the flow and its geometry, yielding unprecedented insight into the inner accreting regions, the effects of strong field gravity on the material within them and the powerful outflows which are driven by the accretion process. }, author = {Rosa, Alessandra De and Uttley, Phil and Gou, LiJun and Liu, Yuan and Bambi, Cosimo and Barret, Didier and Belloni, Tomaso and Berti, Emanuele and Bianchi, Stefano and Caiazzo, Ilaria and Casella, Piergiorgio and Feroci, Marco and Ferrari, Valeria and Gualtieri, Leonardo and Heyl, Jeremy and Ingram, Adam and Karas, Vladimir and Lu, FangJun and Luo, Bin and Matt, Giorgio and Motta, Sara and Neilsen, Joseph and Pani, Paolo and Santangelo, Andrea and Shu, XinWen and Wang, JunFeng and Wang, Jian-Min and Xue, YongQuan and Xu, YuPeng and Yuan, WeiMin and Yuan, YeFei and Zhang, Shuang-Nan and Zhang, Shu and Agudo, Ivan and Amati, Lorenzo and Andersson, Nils and Baglio, Cristina and Bakala, Pavel and Baykal, Altan and Bhattacharyya, Sudip and Bombaci, Ignazio and Bucciantini, Niccoló and Capitanio, Fiamma and Ciolfi, Riccardo and Cui, Wei K. and D’Ammando, Filippo and Dauser, Thomas and Del Santo, Melania and De Marco, Barbara and Di Salvo, Tiziana and Done, Chris and Dovčiak, Michal and Fabian, Andrew C. and Falanga, Maurizio and Gambino, Angelo Francesco and Gendre, Bruce and Grinberg, Victoria and Heger, Alexander and Homan, Jeroen and Iaria, Rosario and Jiang, JiaChen and Jin, ChiChuan and Koerding, Elmar and Linares, Manu and Liu, Zhu and Maccarone, Thomas J. and Malzac, Julien and Manousakis, Antonios and Marin, Frédéric and Marinucci, Andrea and Mehdipour, Missagh and Méndez, Mariano and Migliari, Simone and Miller, Cole and Miniutti, Giovanni and Nardini, Emanuele and O’Brien, Paul T. and Osborne, Julian P. and Petrucci, Pierre Olivier and Possenti, Andrea and Riggio, Alessandro and Rodriguez, Jerome and Sanna, Andrea and Shao, LiJing and Sobolewska, Malgosia and Sramkova, Eva and Stevens, Abigail L. and Stiele, Holger and Stratta, Giulia and Stuchlik, Zdenek and Svoboda, Jiri and Tamburini, Fabrizio and Tauris, Thomas M. and Tombesi, Francesco and Torok, Gabriel and Urbanec, Martin and Vincent, Frederic and Wu, QingWen and Yuan, Feng and in’ t Zand, Jean J. M. and Zdziarski, Andrzej A. and Zhou, XinLin}, issn = {1869-1927}, journal = {Science China Physics, Mechanics & Astronomy}, keywords = {General Physics and Astronomy}, number = {2}, publisher = {Springer Nature}, title = {{Accretion in strong field gravity with eXTP}}, doi = {10.1007/s11433-018-9297-0}, volume = {62}, year = {2018}, } @article{15233, abstract = {In this paper we present the science potential of the enhanced X-ray Timing and Polarimetry (eXTP) mission for studies of strongly magnetized objects. We will focus on the physics and astrophysics of strongly magnetized objects, namely magnetars, accreting X-ray pulsars, and rotation powered pulsars. We also discuss the science potential of eXTP for QED studies. Developed by an international Consortium led by the Institute of High Energy Physics of the Chinese Academy of Sciences, the eXTP mission is expected to be launched in the mid 2020s.}, author = {Santangelo, Andrea and Zane, Silvia and Feng, Hua and Xu, RenXin and Doroshenko, Victor and Bozzo, Enrico and Caiazzo, Ilaria and Zelati, Francesco Coti and Esposito, Paolo and González-Caniulef, Denis and Heyl, Jeremy and Huppenkothen, Daniela and Israel, Gianluca and Li, ZhaoSheng and Lin, Lin and Mignani, Roberto and Rea, Nanda and Orlandini, Mauro and Taverna, Roberto and Tong, Hao and Turolla, Roberto and Baglio, Cristina and Bernardini, Federico and Bucciantini, Niccolo’ and Feroci, Marco and Fürst, Felix and Göğüş, Ersin and Güngör, Can and Ji, Long and Lu, FangJun and Manousakis, Antonios and Mereghetti, Sandro and Mikusincova, Romana and Paul, Biswajit and Prescod-Weinstein, Chanda and Younes, George and Tiengo, Andrea and Xu, YuPeng and Watts, Anna and Zhang, Shu and Zhan, Shuang-Nan}, issn = {1869-1927}, journal = {Science China Physics, Mechanics & Astronomy}, keywords = {General Physics and Astronomy}, number = {2}, publisher = {Springer Nature}, title = {{Physics and astrophysics of strong magnetic field systems with eXTP}}, doi = {10.1007/s11433-018-9234-3}, volume = {62}, year = {2018}, } @article{10626, abstract = {Owing to their wide tunability, multiple internal degrees of freedom, and low disorder, graphene heterostructures are emerging as a promising experimental platform for fractional quantum Hall (FQH) studies. Here, we report FQH thermal activation gap measurements in dual graphite-gated monolayer graphene devices fabricated in an edgeless Corbino geometry. In devices with substrate-induced sublattice splitting, we find a tunable crossover between single- and multicomponent FQH states in the zero energy Landau level. Activation gaps in the single-component regime show excellent agreement with numerical calculations using a single broadening parameter Γ≈7.2K. In the first excited Landau level, in contrast, FQH gaps are strongly influenced by Landau level mixing, and we observe an unexpected valley-ordered state at integer filling ν=−4.}, author = {Polshyn, Hryhoriy and Zhou, H. and Spanton, E. M. and Taniguchi, T. and Watanabe, K. and Young, A. F.}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {general physics and astronomy}, number = {22}, publisher = {American Physical Society}, title = {{Quantitative transport measurements of fractional quantum Hall energy gaps in edgeless graphene devices}}, doi = {10.1103/physrevlett.121.226801}, volume = {121}, year = {2018}, } @article{10362, abstract = {Nuclear pore complexes (NPCs) form gateways that control molecular exchange between the nucleus and the cytoplasm. They impose a diffusion barrier to macromolecules and enable the selective transport of nuclear transport receptors with bound cargo. The underlying mechanisms that establish these permeability properties remain to be fully elucidated but require unstructured nuclear pore proteins rich in Phe-Gly (FG)-repeat domains of different types, such as FxFG and GLFG. While physical modeling and in vitro approaches have provided a framework for explaining how the FG network contributes to the barrier and transport properties of the NPC, it remains unknown whether the number and/or the spatial positioning of different FG-domains along a cylindrical, ∼40 nm diameter transport channel contributes to their collective properties and function. To begin to answer these questions, we have used DNA origami to build a cylinder that mimics the dimensions of the central transport channel and can house a specified number of FG-domains at specific positions with easily tunable design parameters, such as grafting density and topology. We find the overall morphology of the FG-domain assemblies to be dependent on their chemical composition, determined by the type and density of FG-repeat, and on their architectural confinement provided by the DNA cylinder, largely consistent with here presented molecular dynamics simulations based on a coarse-grained polymer model. In addition, high-speed atomic force microscopy reveals local and reversible FG-domain condensation that transiently occludes the lumen of the DNA central channel mimics, suggestive of how the NPC might establish its permeability properties.}, author = {Fisher, Patrick D. Ellis and Shen, Qi and Akpinar, Bernice and Davis, Luke K. and Chung, Kenny Kwok Hin and Baddeley, David and Šarić, Anđela and Melia, Thomas J. and Hoogenboom, Bart W. and Lin, Chenxiang and Lusk, C. Patrick}, issn = {1936-086X}, journal = {ACS Nano}, keywords = {general physics and astronomy}, number = {2}, pages = {1508--1518}, publisher = {American Chemical Society}, title = {{A Programmable DNA origami platform for organizing intrinsically disordered nucleoporins within nanopore confinement}}, doi = {10.1021/acsnano.7b08044}, volume = {12}, year = {2018}, } @article{8419, abstract = {In this survey, we provide a concise introduction to convex billiards and describe some recent results, obtained by the authors and collaborators, on the classification of integrable billiards, namely the so-called Birkhoff conjecture. This article is part of the theme issue ‘Finite dimensional integrable systems: new trends and methods’.}, author = {Kaloshin, Vadim and Sorrentino, Alfonso}, issn = {1364-503X}, journal = {Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences}, keywords = {General Engineering, General Physics and Astronomy, General Mathematics}, number = {2131}, publisher = {The Royal Society}, title = {{On the integrability of Birkhoff billiards}}, doi = {10.1098/rsta.2017.0419}, volume = {376}, year = {2018}, } @article{8420, abstract = {We show that in the space of all convex billiard boundaries, the set of boundaries with rational caustics is dense. More precisely, the set of billiard boundaries with caustics of rotation number 1/q is polynomially sense in the smooth case, and exponentially dense in the analytic case.}, author = {Kaloshin, Vadim and Zhang, Ke}, issn = {0951-7715}, journal = {Nonlinearity}, keywords = {Mathematical Physics, General Physics and Astronomy, Applied Mathematics, Statistical and Nonlinear Physics}, number = {11}, pages = {5214--5234}, publisher = {IOP Publishing}, title = {{Density of convex billiards with rational caustics}}, doi = {10.1088/1361-6544/aadc12}, volume = {31}, year = {2018}, } @article{14004, abstract = {High-harmonic spectroscopy driven by circularly polarized laser pulses and their counterrotating second harmonic is a new branch of attosecond science which currently lacks quantitative interpretations. We extend this technique to the midinfrared regime and record detailed high-harmonic spectra of several rare-gas atoms. These results are compared with the solution of the Schrödinger equation in three dimensions and calculations based on the strong-field approximation that incorporate accurate scattering-wave recombination matrix elements. A quantum-orbit analysis of these results provides a transparent interpretation of the measured intensity ratios of symmetry-allowed neighboring harmonics in terms of (i) a set of propensity rules related to the angular momentum of the atomic orbitals, (ii) atom-specific matrix elements related to their electronic structure, and (iii) the interference of the emissions associated with electrons in orbitals corotating or counterrotating with the laser fields. These results provide the foundation for a quantitative understanding of bicircular high-harmonic spectroscopy.}, author = {Baykusheva, Denitsa Rangelova and Brennecke, Simon and Lein, Manfred and Wörner, Hans Jakob}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {General Physics and Astronomy}, number = {20}, publisher = {American Physical Society}, title = {{Signatures of electronic structure in bicircular high-harmonic spectroscopy}}, doi = {10.1103/physrevlett.119.203201}, volume = {119}, year = {2017}, } @article{14005, abstract = {Strong-field photoelectron holography and laser-induced electron diffraction (LIED) are two powerful emerging methods for probing the ultrafast dynamics of molecules. However, both of them have remained restricted to static systems and to nuclear dynamics induced by strong-field ionization. Here we extend these promising methods to image purely electronic valence-shell dynamics in molecules using photoelectron holography. In the same experiment, we use LIED and photoelectron holography simultaneously, to observe coupled electronic-rotational dynamics taking place on similar timescales. These results offer perspectives for imaging ultrafast dynamics of molecules on femtosecond to attosecond timescales.}, author = {Walt, Samuel G. and Bhargava Ram, Niraghatam and Atala, Marcos and Shvetsov-Shilovski, Nikolay I and von Conta, Aaron and Baykusheva, Denitsa Rangelova and Lein, Manfred and Wörner, Hans Jakob}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary}, publisher = {Springer Nature}, title = {{Dynamics of valence-shell electrons and nuclei probed by strong-field holography and rescattering}}, doi = {10.1038/ncomms15651}, volume = {8}, year = {2017}, } @article{14006, abstract = {We present a theoretical formalism for the calculation of attosecond delays in molecular photoionization. It is shown how delays relevant to one-photon-ionization, also known as Eisenbud-Wigner-Smith delays, can be obtained from the complex dipole matrix elements provided by molecular quantum scattering theory. These results are used to derive formulae for the delays measured by two-photon attosecond interferometry based on an attosecond pulse train and a dressing femtosecond infrared pulse. These effective delays are first expressed in the molecular frame where maximal information about the molecular photoionization dynamics is available. The effects of averaging over the emission direction of the electron and the molecular orientation are introduced analytically. We illustrate this general formalism for the case of two polyatomic molecules. N2O serves as an example of a polar linear molecule characterized by complex photoionization dynamics resulting from the presence of molecular shape resonances. H2O illustrates the case of a non-linear molecule with comparably simple photoionization dynamics resulting from a flat continuum. Our theory establishes the foundation for interpreting measurements of the photoionization dynamics of all molecules by attosecond metrology.}, author = {Baykusheva, Denitsa Rangelova and Wörner, Hans Jakob}, issn = {1089-7690}, journal = {The Journal of Chemical Physics}, keywords = {Physical and Theoretical Chemistry, General Physics and Astronomy}, number = {12}, publisher = {AIP Publishing}, title = {{Theory of attosecond delays in molecular photoionization}}, doi = {10.1063/1.4977933}, volume = {146}, year = {2017}, } @article{14031, abstract = {High-harmonic spectroscopy driven by circularly polarized laser pulses and their counterrotating second harmonic is a new branch of attosecond science which currently lacks quantitative interpretations. We extend this technique to the midinfrared regime and record detailed high-harmonic spectra of several rare-gas atoms. These results are compared with the solution of the Schrödinger equation in three dimensions and calculations based on the strong-field approximation that incorporate accurate scattering-wave recombination matrix elements. A quantum-orbit analysis of these results provides a transparent interpretation of the measured intensity ratios of symmetry-allowed neighboring harmonics in terms of (i) a set of propensity rules related to the angular momentum of the atomic orbitals, (ii) atom-specific matrix elements related to their electronic structure, and (iii) the interference of the emissions associated with electrons in orbitals corotating or counterrotating with the laser fields. These results provide the foundation for a quantitative understanding of bicircular high-harmonic spectroscopy.}, author = {Baykusheva, Denitsa Rangelova and Brennecke, Simon and Lein, Manfred and Wörner, Hans Jakob}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {General Physics and Astronomy}, number = {20}, publisher = {American Physical Society}, title = {{Signatures of electronic structure in bicircular high-harmonic spectroscopy}}, doi = {10.1103/physrevlett.119.203201}, volume = {119}, year = {2017}, } @article{11065, abstract = {Premature aging disorders provide an opportunity to study the mechanisms that drive aging. In Hutchinson-Gilford progeria syndrome (HGPS), a mutant form of the nuclear scaffold protein lamin A distorts nuclei and sequesters nuclear proteins. We sought to investigate protein homeostasis in this disease. Here, we report a widespread increase in protein turnover in HGPS-derived cells compared to normal cells. We determine that global protein synthesis is elevated as a consequence of activated nucleoli and enhanced ribosome biogenesis in HGPS-derived fibroblasts. Depleting normal lamin A or inducing mutant lamin A expression are each sufficient to drive nucleolar expansion. We further show that nucleolar size correlates with donor age in primary fibroblasts derived from healthy individuals and that ribosomal RNA production increases with age, indicating that nucleolar size and activity can serve as aging biomarkers. While limiting ribosome biogenesis extends lifespan in several systems, we show that increased ribosome biogenesis and activity are a hallmark of premature aging.}, author = {Buchwalter, Abigail and HETZER, Martin W}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry}, publisher = {Springer Nature}, title = {{Nucleolar expansion and elevated protein translation in premature aging}}, doi = {10.1038/s41467-017-00322-z}, volume = {8}, year = {2017}, } @article{14010, abstract = {We report measurements of energy-dependent attosecond photoionization delays between the two outer-most valence shells of N2O and H2O. The combination of single-shot signal referencing with the use of different metal foils to filter the attosecond pulse train enables us to extract delays from congested spectra. Remarkably large delays up to 160 as are observed in N2O, whereas the delays in H2O are all smaller than 50 as in the photon-energy range of 20-40 eV. These results are interpreted by developing a theory of molecular photoionization delays. The long delays measured in N2O are shown to reflect the population of molecular shape resonances that trap the photoelectron for a duration of up to ∼110 as. The unstructured continua of H2O result in much smaller delays at the same photon energies. Our experimental and theoretical methods make the study of molecular attosecond photoionization dynamics accessible.}, author = {Huppert, Martin and Jordan, Inga and Baykusheva, Denitsa Rangelova and von Conta, Aaron and Wörner, Hans Jakob}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {General Physics and Astronomy}, number = {9}, publisher = {American Physical Society}, title = {{Attosecond delays in molecular photoionization}}, doi = {10.1103/physrevlett.117.093001}, volume = {117}, year = {2016}, } @article{14011, abstract = {We introduce bicircular high-harmonic spectroscopy as a new method to probe dynamical symmetries of atoms and molecules and their evolution in time. Our approach is based on combining a circularly polarized femtosecond fundamental field of frequency ω with its counterrotating second harmonic 2ω. We demonstrate the ability of bicircular high-harmonic spectroscopy to characterize the orbital angular momentum symmetry of atomic orbitals. We further show that breaking the threefold rotational symmetry of the generating medium-at the level of either the ensemble or that of a single molecule-results in the emission of the otherwise parity-forbidden frequencies 3qω  (q∈N), which provide a background-free probe of dynamical molecular symmetries.}, author = {Baykusheva, Denitsa Rangelova and Ahsan, Md Sabbir and Lin, Nan and Wörner, Hans Jakob}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {General Physics and Astronomy}, number = {12}, publisher = {American Physical Society}, title = {{Bicircular high-harmonic spectroscopy reveals dynamical symmetries of atoms and molecules}}, doi = {10.1103/physrevlett.116.123001}, volume = {116}, year = {2016}, } @article{11072, abstract = {Spatiotemporal activation of RhoA and actomyosin contraction underpins cellular adhesion and division. Loss of cell–cell adhesion and chromosomal instability are cardinal events that drive tumour progression. Here, we show that p120-catenin (p120) not only controls cell–cell adhesion, but also acts as a critical regulator of cytokinesis. We find that p120 regulates actomyosin contractility through concomitant binding to RhoA and the centralspindlin component MKLP1, independent of cadherin association. In anaphase, p120 is enriched at the cleavage furrow where it binds MKLP1 to spatially control RhoA GTPase cycling. Binding of p120 to MKLP1 during cytokinesis depends on the N-terminal coiled-coil domain of p120 isoform 1A. Importantly, clinical data show that loss of p120 expression is a common event in breast cancer that strongly correlates with multinucleation and adverse patient survival. In summary, our study identifies p120 loss as a driver event of chromosomal instability in cancer. }, author = {van de Ven, Robert A.H. and de Groot, Jolien S. and Park, Danielle and van Domselaar, Robert and de Jong, Danielle and Szuhai, Karoly and van der Wall, Elsken and Rueda, Oscar M. and Ali, H. Raza and Caldas, Carlos and van Diest, Paul J. and HETZER, Martin W and Sahai, Erik and Derksen, Patrick W.B.}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry}, publisher = {Springer Nature}, title = {{p120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis}}, doi = {10.1038/ncomms13874}, volume = {7}, year = {2016}, } @article{10376, abstract = {Nucleation processes are at the heart of a large number of phenomena, from cloud formation to protein crystallization. A recently emerging area where nucleation is highly relevant is the initiation of filamentous protein self-assembly, a process that has broad implications in many research areas ranging from medicine to nanotechnology. As such, spontaneous nucleation of protein fibrils has received much attention in recent years with many theoretical and experimental studies focusing on the underlying physical principles. In this paper we make a step forward in this direction and explore the early time behaviour of filamentous protein growth in the context of nucleation theory. We first provide an overview of the thermodynamics and kinetics of spontaneous nucleation of protein filaments in the presence of one relevant degree of freedom, namely the cluster size. In this case, we review how key kinetic observables, such as the reaction order of spontaneous nucleation, are directly related to the physical size of the critical nucleus. We then focus on the increasingly prominent case of filament nucleation that includes a conformational conversion of the nucleating building-block as an additional slow step in the nucleation process. Using computer simulations, we study the concentration dependence of the nucleation rate. We find that, under these circumstances, the reaction order of spontaneous nucleation with respect to the free monomer does no longer relate to the overall physical size of the nucleating aggregate but rather to the portion of the aggregate that actively participates in the conformational conversion. Our results thus provide a novel interpretation of the common kinetic descriptors of protein filament formation, including the reaction order of the nucleation step or the scaling exponent of lag times, and put into perspective current theoretical descriptions of protein aggregation.}, author = {Šarić, Anđela and Michaels, Thomas C. T. and Zaccone, Alessio and Knowles, Tuomas P. J. and Frenkel, Daan}, issn = {1089-7690}, journal = {The Journal of Chemical Physics}, keywords = {physical and theoretical chemistry, general physics and astronomy}, number = {21}, publisher = {American Institute of Physics}, title = {{Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation}}, doi = {10.1063/1.4965040}, volume = {145}, year = {2016}, } @article{10378, abstract = {The ability of biological molecules to replicate themselves is the foundation of life, requiring a complex cellular machinery. However, a range of aberrant processes involve the self-replication of pathological protein structures without any additional assistance. One example is the autocatalytic generation of pathological protein aggregates, including amyloid fibrils, involved in neurodegenerative disorders. Here, we use computer simulations to identify the necessary requirements for the self-replication of fibrillar assemblies of proteins. We establish that a key physical determinant for this process is the affinity of proteins for the surfaces of fibrils. We find that self-replication can take place only in a very narrow regime of inter-protein interactions, implying a high level of sensitivity to system parameters and experimental conditions. We then compare our theoretical predictions with kinetic and biosensor measurements of fibrils formed from the Aβ peptide associated with Alzheimer’s disease. Our results show a quantitative connection between the kinetics of self-replication and the surface coverage of fibrils by monomeric proteins. These findings reveal the fundamental physical requirements for the formation of supra-molecular structures able to replicate themselves, and shed light on mechanisms in play in the proliferation of protein aggregates in nature.}, author = {Šarić, Anđela and Buell, Alexander K. and Meisl, Georg and Michaels, Thomas C. T. and Dobson, Christopher M. and Linse, Sara and Knowles, Tuomas P. J. and Frenkel, Daan}, issn = {1745-2481}, journal = {Nature Physics}, keywords = {general physics and astronomy}, number = {9}, pages = {874--880}, publisher = {Springer Nature}, title = {{Physical determinants of the self-replication of protein fibrils}}, doi = {10.1038/nphys3828}, volume = {12}, year = {2016}, }