Publications by authors named "Ana-Sunčana Smith"

47 Publications

From Water Solutions to Ionic Liquids with Solid State Nanopores as a Perspective to Study Transport and Translocation Phenomena.

Small 2021 May 6:e2100777. Epub 2021 May 6.

Group for Computational Life Sciences, Ruđer Bošković Institute, Division of Physical Chemistry, 10000, Zagreb, Croatia.

Solid state nanopores are single-molecular devices governed by nanoscale physics with a broad potential for technological applications. However, the control of translocation speed in these systems is still limited. Ionic liquids are molten salts which are commonly used as alternate solvents enabling the regulation of the chemical and physical interactions on solid-liquid interfaces. While their combination can be challenging to the understanding of nanoscopic processes, there has been limited attempts on bringing these two together. While summarizing the state of the art and open questions in these fields, several major advances are presented with a perspective on the next steps in the investigations of ionic-liquid filled nanopores, both from a theoretical and experimental standpoint. By analogy to aqueous solutions, it is argued that ionic liquids and nanopores can be combined to provide new nanofluidic functionalities, as well as to help resolve some of the pertinent problems in understanding transport phenomena in confined ionic liquids and providing better control of the speed of translocating analytes.
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http://dx.doi.org/10.1002/smll.202100777DOI Listing
May 2021

On the control of dispersion interactions between biological membranes and protein coated biointerfaces.

J Colloid Interface Sci 2021 Mar 11;598:464-473. Epub 2021 Mar 11.

PULS Group, Department of Physics and Interdisciplinary Center for Nanostructured Films, Friedrich-Alexander-Universität Erlangen-Nürnberg, IZNF, Cauerstrasse 3, 91058 Erlangen, Germany; Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia. Electronic address:

Hypothesis: Interaction of cellular membranes with biointerfaces is of vital importance for a number of medical devices and implants. Adhesiveness of these surfaces and cells is often regulated by depositing a layer of bovine serum albumin (BSA) or other protein coatings. However, anomalously large separations between phospholipid membranes and the biointerfaces in various conditions and buffers have been observed, which could not be understood using available theoretical arguments.

Methods: Using the Lifshitz theory, we here evaluate the distance-dependent Hamaker coefficient describing the dispersion interaction between a biointerface and a membrane to understand the relative positioning of two surfaces. Our theoretical modeling is supported by experiments where the biointerface is represented by a glass substrate with deposited BSA and protein layers. These biointerfaces are allowed to interact with giant unilamellar vesicles decorated with polyethylene glycol (PEG) using PEG lipids to mimic cellular membranes and their pericellular coat.

Results: We demonstrate that careful treatment of the van der Waals interactions is critical for explaining the lack of adhesiveness of the membranes with protein-decorated biointerfaces. We show that BSA alone indeed passivates the glass, but depositing an additional protein layer on the surface BSA, or producing multiple layers of proteins and BSA results in repulsive dispersion forces responsible for 100 nm large equilibrium separations between the two surfaces.
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http://dx.doi.org/10.1016/j.jcis.2021.02.078DOI Listing
March 2021

Molecular Biomechanics Controls Protein Mixing and Segregation in Adherent Membranes.

Int J Mol Sci 2021 Apr 2;22(7). Epub 2021 Apr 2.

PULS Group, Institute for Theoretical Physics and Interdisciplinary Center for Nanostructured Films, Friedrich-Alexander-University Erlangen-Nürnberg, Cauerstrasse 3, 91058 Erlangen, Germany.

Cells interact with their environment by forming complex structures involving a multitude of proteins within assemblies in the plasma membrane. Despite the omnipresence of these assemblies, a number of questions about the correlations between the organisation of domains and the biomechanical properties of the involved proteins, namely their length, flexibility and affinity, as well as about the coupling to the elastic, fluctuating membrane, remain open. Here we address these issues by developing an effective Kinetic Monte Carlo simulation to model membrane adhesion. We apply this model to a typical experiment in which a cell binds to a functionalized solid supported bilayer and use two ligand-receptor pairs to study these couplings. We find that differences in affinity and length of proteins forming adhesive contacts result in several characteristic features in the calculated phase diagrams. One such feature is mixed states occurring even with proteins with length differences of 10 nm. Another feature are stable nanodomains with segregated proteins appearing on time scales of cell experiments, and for biologically relevant parameters. Furthermore, we show that macroscopic ring-like patterns can spontaneously form as a consequence of emergent protein fluxes. The capacity to form domains is captured by an order parameter that is founded on the virial coefficients for the membrane mediated interactions between bonds, which allow us to collapse all the data. These findings show that taking into account the role of the membrane allows us to recover a number of experimentally observed patterns. This is an important perspective in the context of explicit biological systems, which can now be studied in significant detail.
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http://dx.doi.org/10.3390/ijms22073699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037219PMC
April 2021

Regimes of motion of magnetocapillary swimmers.

Eur Phys J E Soft Matter 2021 Apr 24;44(4):59. Epub 2021 Apr 24.

Helmholtz Institute Erlangen-Nürnberg for Renewable Energy (IEK-11), Forschungszentrum Jülich, Fürther Straße 248, 90429, Nuremberg, Germany.

The dynamics of a triangular magnetocapillary swimmer is studied using the lattice Boltzmann method. We extend on our previous work, which deals with the self-assembly and a specific type of the swimmer motion characterized by the swimmer's maximum velocity centred around the particle's inverse viscous time. Here, we identify additional regimes of motion. First, modifying the ratio of surface tension and magnetic forces allows to study the swimmer propagation in the regime of significantly lower frequencies mainly defined by the strength of the magnetocapillary potential. Second, introducing a constant magnetic contribution in each of the particles in addition to their magnetic moment induced by external fields leads to another regime characterized by strong in-plane swimmer reorientations that resemble experimental observations.
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http://dx.doi.org/10.1140/epje/s10189-021-00065-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068718PMC
April 2021

Recent Advances and Prospects in the Research of Nascent Adhesions.

Front Physiol 2020 4;11:574371. Epub 2020 Dec 4.

PULS Group, Institute for Theoretical Physics, Interdisciplinary Center for Nanostructured Films, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.

Nascent adhesions are submicron transient structures promoting the early adhesion of cells to the extracellular matrix. Nascent adhesions typically consist of several tens of integrins, and serve as platforms for the recruitment and activation of proteins to build mature focal adhesions. They are also associated with early stage signaling and the mechanoresponse. Despite their crucial role in sampling the local extracellular matrix, very little is known about the mechanism of their formation. Consequently, there is a strong scientific activity focused on elucidating the physical and biochemical foundation of their development and function. Precisely the results of this effort will be summarized in this article.
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http://dx.doi.org/10.3389/fphys.2020.574371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746844PMC
December 2020

Maturation of Monocyte-Derived DCs Leads to Increased Cellular Stiffness, Higher Membrane Fluidity, and Changed Lipid Composition.

Front Immunol 2020 27;11:590121. Epub 2020 Nov 27.

Laboratory of Dendritic Cell Biology, Department of Dermatology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), University Hospital Erlangen, Erlangen, Germany.

Dendritic cells (DCs) are professional antigen-presenting cells of the immune system. Upon sensing pathogenic material in their environment, DCs start to mature, which includes cellular processes, such as antigen uptake, processing and presentation, as well as upregulation of costimulatory molecules and cytokine secretion. During maturation, DCs detach from peripheral tissues, migrate to the nearest lymph node, and find their way into the correct position in the net of the lymph node microenvironment to meet and interact with the respective T cells. We hypothesize that the maturation of DCs is well prepared and optimized leading to processes that alter various cellular characteristics from mechanics and metabolism to membrane properties. Here, we investigated the mechanical properties of monocyte-derived dendritic cells (moDCs) using real-time deformability cytometry to measure cytoskeletal changes and found that mature moDCs were stiffer compared to immature moDCs. These cellular changes likely play an important role in the processes of cell migration and T cell activation. As lipids constitute the building blocks of the plasma membrane, which, during maturation, need to adapt to the environment for migration and DC-T cell interaction, we performed an unbiased high-throughput lipidomics screening to identify the lipidome of moDCs. These analyses revealed that the overall lipid composition was significantly changed during moDC maturation, even implying an increase of storage lipids and differences of the relative abundance of membrane lipids upon maturation. Further, metadata analyses demonstrated that lipid changes were associated with the serum low-density lipoprotein (LDL) and cholesterol levels in the blood of the donors. Finally, using lipid packing imaging we found that the membrane of mature moDCs revealed a higher fluidity compared to immature moDCs. This comprehensive and quantitative characterization of maturation associated changes in moDCs sets the stage for improving their use in clinical application.
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http://dx.doi.org/10.3389/fimmu.2020.590121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728921PMC
November 2020

Quantitative Structural Organization of Bulk Apical Membrane Traffic in Pollen Tubes.

Plant Physiol 2020 08 1;183(4):1559-1585. Epub 2020 Jun 1.

Cell Biology, Department of Biology, Friedrich-Alexander-University Erlangen Nuremberg, 91058 Erlangen, Germany

Pollen tube tip growth depends on balancing secretion of cell wall material with endocytic recycling of excess material incorporated into the plasma membrane (PM). The classical model of tip growth, which predicts bulk secretion, occurs apically, and is compensated by subapical endocytosis, has been challenged in recent years. Many signaling proteins and lipids with important functions in the regulation of membrane traffic underlying tip growth associate with distinct regions of the pollen tube PM, and understanding the mechanisms responsible for the targeting of these regulatory factors to specific PM domains requires quantitative information concerning the sites of bulk secretion and endocytosis. Here, we quantitatively characterized the spatial organization of membrane traffic during tip growth by analyzing steady-state distributions and dynamics of FM4-64-labeled lipids and YFP-tagged transmembrane (TM) proteins in tobacco () pollen tubes growing normally or treated with Brefeldin A to block secretion. We established that (1) secretion delivers TM proteins and recycled membrane lipids to the same apical PM domain, and (2) FM4-64-labeled lipids, but not the analyzed TM proteins, undergo endocytic recycling within a clearly defined subapical region. We mathematically modeled the steady-state PM distributions of all analyzed markers to better understand differences between them and to support the experimental data. Finally, we mapped subapical F-actin fringe and trans-Golgi network positioning relative to sites of bulk secretion and endocytosis to further characterize functions of these structures in apical membrane traffic. Our results support and further define the classical model of apical membrane traffic at the tip of elongating pollen tubes.
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http://dx.doi.org/10.1104/pp.20.00380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401101PMC
August 2020

Structural characterization of an ionic liquid in bulk and in nano-confined environment using data from MD simulations.

Data Brief 2020 Feb 23;28:104794. Epub 2019 Nov 23.

Group for Computational Life Sciences, Department of Physical Chemistry, Ruđer Bošković Institute, Bijenička 54, 10000, Zagreb, Croatia.

This article contains data on structural characterization of the [C2Mim][NTf2] in bulk and in nano-confined environment obtained using MD simulations. These data supplement those presented in the paper "Insights from Molecular Dynamics Simulations on Structural Organization and Diffusive Dynamics of an Ionic Liquid at Solid and Vacuum Interfaces" [1], where force fields with three different charge methods and three charge scaling factors were used for the analysis of the IL in the bulk, at the interface with the vacuum and the IL film in the contact with a hydroxylated alumina surface. Here, we present details on the construction of the model systems in an extended detailed methods section. Furthermore, for best parametrization, structural and dynamic properties of IL in different environment are studied with certain features presented herein.
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http://dx.doi.org/10.1016/j.dib.2019.104794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909096PMC
February 2020

Correction: Capillary assemblies in a rotating magnetic field.

Soft Matter 2019 Dec 12;15(45):9376. Epub 2019 Nov 12.

GRASP Lab, CESAM Research Unit, University of Liège, B-4000 Liège, Belgium.

Correction for 'Capillary assemblies in a rotating magnetic field' by Galien Grosjean et al., Soft Matter, 2019, DOI: .
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http://dx.doi.org/10.1039/c9sm90230aDOI Listing
December 2019

Capillary assemblies in a rotating magnetic field.

Soft Matter 2019 Nov 29;15(44):9093-9103. Epub 2019 Oct 29.

GRASP Lab, CESAM Research Unit, University of Liège, B-4000 Liège, Belgium.

Small objects floating on a fluid have a tendency to aggregate due to capillary forces. This effect has been used, with the help of a magnetic induction field, to assemble submillimeter metallic spheres into a variety of structures, whose shape and size can be tuned. Under time-varying fields, these assemblies can propel themselves due to a breaking of time reversal symmetry in their adopted shapes. In this article, we study the influence of an in-plane rotation of the magnetic field on these structures. Various rotational modes have been observed with different underlying mechanisms. The magnetic properties of the particles cause them to rotate individually. Dipole-dipole interactions in the assembly can cause the whole structure to align with the field. Finally, non-reciprocal deformations can power the rotation of the assembly. Symmetry plays an important role in the dynamics, as well as the frequency and amplitude of the applied field. Understanding the interplay of these effects is essential, both to explain previous observations and to develop new functions for these assemblies.
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http://dx.doi.org/10.1039/c9sm01414dDOI Listing
November 2019

Geometric effects in random assemblies of ellipses.

Soft Matter 2019 Oct;15(42):8566-8577

Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia.

Assemblies of anisotropic particles commonly appear in studies of active many-body systems. However, in two dimensions, the geometric ramifications of the finite density of such objects are not entirely understood. To fully characterize these effects, we perform an in-depth study of random assemblies generated by a slow compression of frictionless elliptical particles. The obtained configurations are then analysed using the Set Voronoi tessellation, which takes the particle shape into account. Not only do we analyse most scalar and vectorial morphological measures, which are commonly discussed in the literature or which have recently been addressed in experiments, but we also systematically explore the correlations between them. While in a limited range of parameters similarities with findings in 3D assemblies could be identified, important differences are found when a broad range of aspect ratios and packing fractions are considered. The data discussed in this study should thus provide a unique reference set such that geometric effects and differences from random assemblies could be clearly identified in more complex systems, including ones with soft and active particles that are typically found in biological systems.
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http://dx.doi.org/10.1039/c9sm01067jDOI Listing
October 2019

Exploring Reactive Conformations of Coenzyme A during Binding and Unbinding to Pyruvate Formate-Lyase.

J Phys Chem A 2019 Oct 17;123(43):9345-9356. Epub 2019 Oct 17.

Group for Computational Life Sciences, Division for Physical Chemistry , Ruđer Bošković Institute , Bijenička cesta 54 , 10000 Zagreb , Croatia.

Pyruvate formate-lyase (PFL) is a glycyl radical enzyme that converts pyruvate and coenzyme A (CoA) into formate and acetyl-CoA in two half-reactions. Recently, we showed that the acetylation of the PFL active site in the first half-reaction induces subtle conformational changes, leading to the opening of a potential channel for CoA entry. Entry of CoA into the active site is crucial for the second half-reaction, involving the acetyl transfer to CoA, and the completion of the catalytic cycle. Using steered molecular dynamics (SMD) simulations, performed on acetylated and nonacetylated monomeric PFL model systems, we first of all investigate the possible entry/exit pathways of CoA with respect to the active site through the previously identified channel. We then perform umbrella sampling simulations on multiple snapshots from SMD trajectories as well as unrestrained molecular dynamics simulations starting from the final structures obtained from entry SMD, with a view to identifying possible bound states of CoA in the near vicinity of the active site. Detailed study of the unrestrained dissociation processes reveals the presence of stable and reactive bound states of CoA close to the active site, one of which is in an ideal position for triggering the second half-reaction. Examination of the spatial distributions associated with the reactive bound states allows us to discuss the free energy barriers. Umbrella sampling, performed on snapshots from unrestrained dynamics confirms the above findings. The significance of the results for the catalysis are discussed for both acetylated and nonacetylated systems.
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http://dx.doi.org/10.1021/acs.jpca.9b06913DOI Listing
October 2019

Optimal motion of triangular magnetocapillary swimmers.

J Chem Phys 2019 Sep;151(12):124707

Helmholtz Institute Erlangen-Nürnberg for Renewable Energy (IEK-11), Forschungszentrum Jülich, Fürther Straße 248, 90429 Nürnberg, Germany.

A system of ferromagnetic particles trapped at a liquid-liquid interface and subjected to a set of magnetic fields (magnetocapillary swimmers) is studied numerically using a hybrid method combining the pseudopotential lattice Boltzmann method and the discrete element method. After investigating the equilibrium properties of a single, two, and three particles at the interface, we demonstrate a controlled motion of the swimmer formed by three particles. It shows a sharp dependence of the average center-of-mass speed on the frequency of the time-dependent external magnetic field. Inspired by experiments on magnetocapillary microswimmers, we interpret the obtained maxima of the swimmer speed by the optimal frequency centered around the characteristic relaxation time of a spherical particle. It is also shown that the frequency corresponding to the maximum speed grows and the maximum average speed decreases with increasing interparticle distances at moderate swimmer sizes. The findings of our lattice Boltzmann simulations are supported by bead-spring model calculations.
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http://dx.doi.org/10.1063/1.5116860DOI Listing
September 2019

Statistical Mechanics of an Elastically Pinned Membrane: Equilibrium Dynamics and Power Spectrum.

Biophys J 2019 08 9;117(3):542-552. Epub 2019 Jul 9.

PULS Group, Institute for Theoretical Physics and the Interdisciplinary Center for Nanostructured Films, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany; Group for Computational Life Sciences, Division of Physical Chemistry, Institut Ruđer Bošković, Zagreb, Croatia. Electronic address:

In biological settings, membranes typically interact locally with other membranes: the extracellular matrix in the exterior or internal cellular structures such as the cytoskeleton, locally pinning the membrane. Characterizing the dynamical properties of such interactions presents a difficult task. Significant progress has been achieved through simulations and experiments, yet analytical progress in modeling pinned membranes has been impeded by the complexity of governing equations. Here, we circumvent these difficulties by calculating analytically the time-dependent Green's function of the operator governing the dynamics of an elastically pinned membrane in a hydrodynamic surrounding and subject to external forces. This enables us to calculate the equilibrium power spectral density for an overdamped membrane pinned by an elastic, permanently attached spring subject to thermal excitations. By considering the effects of the finite experimental resolution on the measured spectra, we show that the elasticity of the pinning can be extracted from the experimentally measured spectrum. Membrane fluctuations can thus be used as a tool to probe mechanical properties of the underlying structures. Such a tool may be particularly relevant in the context of cell mechanics, in which the elasticity of the membrane's attachment to the cytoskeleton could be measured.
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http://dx.doi.org/10.1016/j.bpj.2019.06.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698198PMC
August 2019

Insights from molecular dynamics simulations on structural organization and diffusive dynamics of an ionic liquid at solid and vacuum interfaces.

J Colloid Interface Sci 2019 Oct 6;553:350-363. Epub 2019 Jun 6.

Group of Computational Life Sciences, Department of Physical Chemistry, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia; PULS Group, Center for Nanostructured Films, Department of Physics, FAU Erlangen-Nürnberg, Cauerstraße 3, 91058, Erlangen, Germany. Electronic address:

Hypothesis: A reliable modelling approach is required for simultaneous characterisation of static and dynamic properties of bulk and interfacial ionic liquids (ILs). This is a prerequisite for a successful investigation of experimentally inaccessible, yet important properties, including those that change significantly with the distance from both vacuum and solid interfaces.

Simulations: We perform molecular dynamics simulations of bulk [CMim][NTf], and thick IL films in contact with vacuum and hydroxylated sapphire surface, using the charge methods CHelpG, RESP-HF and RESP-B3LYP with charge scaling factors 1.0, 0.9 and 0.85.

Findings: By determining and employing appropriate system sizes and simulations lengths, and by benchmarking against self-diffusion coefficients, surface tension, X-ray reflectivity, and structural data, we identify RESP-HF/0.9 as the best non-polarizable force field for this IL. We use this optimal parametrisation to predict novel physical properties of confined IL films. First we fully characterise the internal configurations and orientations of IL molecules relative to, and as a function of the distance from the solid and vacuum interfaces. Second, we evaluate densities together with mobilities in-plane and normal to the interfaces and find that strong correlations between the IL's stratification and diffusive transport in the interfacial layers persist for several nanometres deep into IL films.
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http://dx.doi.org/10.1016/j.jcis.2019.06.017DOI Listing
October 2019

The Influence of Chemical Change on Protein Dynamics: A Case Study with Pyruvate Formate-Lyase.

Chemistry 2019 Jul 9;25(37):8741-8753. Epub 2019 May 9.

Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička 54, Zagreb, Croatia.

Pyruvate formate-lyase (PFL) catalyzes the reversible conversion of pyruvate and coenzyme A (CoA) into formate and acetyl-CoA in two half-reactions. For the second half-reaction to take place, the S-H group of CoA must enter the active site of the enzyme to retrieve a protein-bound acetyl group. However, CoA is bound at the protein surface, whereas the active site is buried in the protein interior, some 20-30 Å away. The PFL system was therefore subjected to a series of extensive molecular dynamics simulations (in the μs range) and a host of advanced analysis procedures. Models representing PFL before and after the first half-reaction were used to examine the possible effect of enzyme acetylation. All simulated structures were found to be relatively stable compared to the initial crystal structure. Although the adenine portion of CoA remained predominantly bound at the protein surface, the binding of the S-H group was significantly more labile. A potential entry channel for CoA, which would allow the S-H group to reach the active site, was identified and characterized. The channel was found to be associated with accentuated fluctuations and a higher probability of being in an open state in acetylated systems. This result suggests that the acetylation of the enzyme assumes a prominent functional role, whereby the formation of the acyl intermediate serves to initiate a subtle signaling cascade that influences the protein dynamics and facilitates the entry of the second substrate.
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http://dx.doi.org/10.1002/chem.201900663DOI Listing
July 2019

Universal hidden order in amorphous cellular geometries.

Nat Commun 2019 02 18;10(1):811. Epub 2019 Feb 18.

Department of Chemistry, Department of Physics, Princeton Institute for the Science and Technology of Materials, and Program in Applied and Computational Mathematics, Princeton University, Princeton, NJ, 08544, USA.

Partitioning space into cells with certain extreme geometrical properties is a central problem in many fields of science and technology. Here we investigate the Quantizer problem, defined as the optimisation of the moment of inertia of Voronoi cells, i.e., similarly-sized 'sphere-like' polyhedra that tile space are preferred. We employ Lloyd's centroidal Voronoi diagram algorithm to solve this problem and find that it converges to disordered states associated with deep local minima. These states are universal in the sense that their structure factors are characterised by a complete independence of a wide class of initial conditions they evolved from. They moreover exhibit an anomalous suppression of long-wavelength density fluctuations and quickly become effectively hyperuniform. Our findings warrant the search for novel amorphous hyperuniform phases and cellular materials with unique physical properties.
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http://dx.doi.org/10.1038/s41467-019-08360-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379405PMC
February 2019

Statistical Mechanics of an Elastically Pinned Membrane: Static Profile and Correlations.

Biophys J 2019 01 8;116(2):283-295. Epub 2018 Dec 8.

PULS Group, Institut für Theoretische Physik and Cluster of Excellence, Engineering of Advanced Materials, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany; Institut Ruđer Bošković, Zagreb, Croatia. Electronic address:

The relation between thermal fluctuations and the mechanical response of a free membrane has been explored in great detail, both theoretically and experimentally. However, understanding this relationship for membranes locally pinned by proteins is significantly more challenging. Given that the coupling of the membrane to the cell cytoskeleton, to the extracellular matrix, and to other internal structures is crucial for the regulation of a number of cellular processes, understanding the role of the pinning is of great interest. In this manuscript, we consider a single protein (elastic spring of a finite rest length) pinning a membrane modeled in the Monge gauge. First, we determine the Green's function for the system and complement this approach by the calculation of the mode-coupling coefficients for the plane wave expansion and the orthonormal fluctuation modes, in turn building a set of tools for numerical and analytic studies of a pinned membrane. Furthermore, we explore static correlations of the free and the pinned membrane, as well as the membrane shape, showing that all three are mutually interdependent and have an identical long-range behavior characterized by the correlation length. Interestingly, the latter displays a nonmonotonic behavior as a function of membrane tension. Importantly, exploiting these relations allows for the experimental determination of the elastic parameters of the pinning. Last but not least, we calculate the interaction potential between two pinning sites and show that even in the absence of the membrane deformation, the pinnings will be subject to an attractive force because of changes in membrane fluctuations.
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http://dx.doi.org/10.1016/j.bpj.2018.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350012PMC
January 2019

Mechanism of the Water-Gas Shift Reaction Catalyzed by Efficient Ruthenium-Based Catalysts: A Computational and Experimental Study.

Angew Chem Int Ed Engl 2019 Jan 12;58(3):741-745. Epub 2018 Dec 12.

Group of Computational Life Sciences, Department of Physical Chemistry, Ruđer Bošković Institute, Bijenička 54, 10000, Zagreb, Croatia.

Supported ionic liquid phase (SILP) catalysis enables a highly efficient, Ru-based, homogeneously catalyzed water-gas shift reaction (WGSR) between 100 °C and 150 °C. The active Ru-complexes have been found to exist in imidazolium chloride melts under operating conditions in a dynamic equilibrium, which is dominated by the [Ru(CO) Cl ] complex. Herein we present state-of-the-art theoretical calculations to elucidate the reaction mechanism in more detail. We show that the mechanism includes the intermediate formation and degradation of hydrogen chloride, which effectively reduces the high barrier for the formation of the requisite dihydrogen complex. The hypothesis that the rate-limiting step involves water is supported by using D O in continuous catalytic WGSR experiments. The resulting mechanism constitutes a highly competitive alternative to earlier reported generic routes involving nucleophilic addition of hydroxide in the gas phase and in solution.
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http://dx.doi.org/10.1002/anie.201811627DOI Listing
January 2019

Structural basis for the shielding function of the dynamic trypanosome variant surface glycoprotein coat.

Nat Microbiol 2017 Nov 11;2(11):1523-1532. Epub 2017 Sep 11.

Department of Cell and Developmental Biology, Theodor-Boveri-Institute, Biocenter, University of Würzburg, 97074, Würzburg, Germany.

The most prominent defence of the unicellular parasite Trypanosoma brucei against the host immune system is a dense coat that comprises a variant surface glycoprotein (VSG). Despite the importance of the VSG family, no complete structure of a VSG has been reported. Making use of high-resolution structures of individual VSG domains, we employed small-angle X-ray scattering to elucidate the first two complete VSG structures. The resulting models imply that the linker regions confer great flexibility between domains, which suggests that VSGs can adopt two main conformations to respond to obstacles and changes of protein density, while maintaining a protective barrier at all times. Single-molecule diffusion measurements of VSG in supported lipid bilayers substantiate this possibility, as two freely diffusing populations could be detected. This translates into a highly flexible overall topology of the surface VSG coat, which displays both lateral movement in the plane of the membrane and variation in the overall thickness of the coat.
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http://dx.doi.org/10.1038/s41564-017-0013-6DOI Listing
November 2017

Measuring the Invisible: Determining the Size of Growing Nanodomains Using the "Inverse FCS".

Biophys J 2017 06;112(11):2245-2246

Laboratoire Physico-Chimie, Institut Curie, CNRS UMR168, Paris-Science Lettres, Université Pierre et Marie Curie-Paris 6, Paris, France.

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http://dx.doi.org/10.1016/j.bpj.2017.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474684PMC
June 2017

Effect of body deformability on microswimming.

Soft Matter 2017 May;13(21):3984-3993

PULS Group, Department of Physics, Friedrich-Alexander-University Erlangen-Nuremberg, Nägelsbachstraße 49b, 91054 Erlangen, Germany.

In this work we consider the following question: given a mechanical microswimming mechanism, does increased deformability of the swimmer body hinder or promote the motility of the swimmer? To answer this we run immersed-boundary-lattice-Boltzmann simulations of a microswimmer composed of deformable beads connected with springs. We find that the same deformations in the beads can result in different effects on the swimming velocity, namely an enhancement or a reduction, depending on the other parameters. To understand this we determine analytically the velocity of the swimmer, starting from the forces driving the motion and assuming that the deformations in the beads are known as functions of time and are much smaller than the beads themselves. We find that to the lowest order, only the driving frequency mode of the surface deformations contributes to the swimming velocity, and comparison to the simulations shows that both the velocity-promoting and velocity-hindering effects of bead deformability are reproduced correctly by the theory in the limit of small bead deformations. For the case of active deformations we show that there are critical values of the spring constant - which for a general swimmer corresponds to its main elastic degree of freedom - which decide whether the body deformability is beneficial for motion or not.
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http://dx.doi.org/10.1039/c7sm00181aDOI Listing
May 2017

Lattice Boltzmann simulations of the bead-spring microswimmer with a responsive stroke-from an individual to swarms.

J Phys Condens Matter 2017 Mar 18;29(12):124001. Epub 2017 Jan 18.

Chair for System Simulation, Friedrich-Alexander University Erlangen-Nürnberg, Cauerstraße 11, 91058 Erlangen, Germany. Cluster of Excellence: EAM, Friedrich-Alexander University Erlangen-Nürnberg, Nägelsbachstraße 49b, 91054 Erlangen, Germany.

Propulsion at low Reynolds numbers is often studied by defining artificial microswimmers which exhibit a particular stroke. The disadvantage of such an approach is that the stroke does not adjust to the environment, in particular the fluid flow, which can diminish the effect of hydrodynamic interactions. To overcome this limitation, we simulate a microswimmer consisting of three beads connected by springs and dampers, using the self-developed waLBerla and [Formula: see text] framework based on the lattice Boltzmann method and the discrete element method. In our approach, the swimming stroke of a swimmer emerges as a balance of the drag, the driving and the elastic internal forces. We validate the simulations by comparing the obtained swimming velocity to the velocity found analytically using a perturbative method where the bead oscillations are taken to be small. Including higher-order terms in the hydrodynamic interactions between the beads improves the agreement to the simulations in parts of the parameter space. Encouraged by the agreement between the theory and the simulations and aided by the massively parallel capabilities of the waLBerla-[Formula: see text] framework, we simulate more than ten thousand such swimmers together, thus presenting the first fully resolved simulations of large swarms with active responsive components.
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http://dx.doi.org/10.1088/1361-648X/aa5a40DOI Listing
March 2017

Limits of Applicability of the Voronoi Tessellation Determined by Centers of Cell Nuclei to Epithelium Morphology.

Front Physiol 2016 25;7:551. Epub 2016 Nov 25.

Physics Underlying Life Sciences Group, Institute for Theoretical Physics and Cluster of Excellence: Engineering of Advanced Materials, Friedrich Alexander University Erlangen-NürnbergErlangen, Germany; Group for Computational Life Sciences, Division of Physical Chemistry, Institute Ruđer BoškovićZagreb, Croatia.

It is well accepted that cells in the tissue can be regarded as tiles tessellating space. A number of approaches were developed to find an appropriate mathematical description of such cell tiling. A particularly useful approach is the so called Voronoi tessellation, built from centers of mass of the cell nuclei (CMVT), which is commonly used for estimating the morphology of cells in epithelial tissues. However, a study providing a statistically sound analysis of this method's accuracy is not available in the literature. We addressed this issue here by comparing a number of morphological measures of the cells, including area, perimeter, and elongation obtained from such a tessellation with identical measures extracted from direct imaging acquired by staining the cell membranes. After analyzing the shapes of 15,000 MDCK II epithelial cells under several conditions, we find that CMVT reasonably well reproduces many of the morphological properties of the tissue with an error that is between 10 and 15%. Moreover, cross-correlations between different morphological measures are reproduced qualitatively correctly by this method. However, all of the properties including the cell perimeters, number of neighbors, and anisotropy measures often suffer from systematic or size dependent errors. These discrepancies originate from the polygonal nature of the tessellation which sets the limits of the applicability of CMVT.
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http://dx.doi.org/10.3389/fphys.2016.00551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122581PMC
November 2016

Nanometric thermal fluctuations of weakly confined biomembranes measured with microsecond time-resolution.

Soft Matter 2016 May;12(21):4755-68

Aix-Marseille Université, CNRS UMR 7325 (Centre Interdisciplinaire de Nanosciences de Marseille - CINaM), Marseille Cedex 9, France.

We probe the bending fluctuations of bio-membranes using highly deflated giant unilamellar vesicles (GUVs) bound to a substrate by a weak potential arising from generic interactions. The substrate is either homogeneous, with GUVs bound only by the weak potential, or is chemically functionalized with a micro-pattern of very strong specific binders. In both cases, the weakly adhered membrane is seen to be confined at a well-defined distance above the surface while it continues to fluctuate strongly. We quantify the fluctuations of the weakly confined membrane at the substrate proximal surface as well as of the free membrane at the distal surface of the same GUV. This strategy enables us to probe in detail the damping of fluctuations in the presence of the substrate, and to independently measure the membrane tension and the strength of the generic interaction potential. Measurements were done using two complementary techniques - dynamic optical displacement spectroscopy (DODS, resolution: 20 nm, 10 μs), and dual wavelength reflection interference contrast microscopy (DW-RICM, resolution: 4 nm, 50 ms). After accounting for the spatio-temporal resolution of the techniques, an excellent agreement between the two measurements was obtained. For both weakly confined systems we explore in detail the link between fluctuations on the one hand and membrane tension and the interaction potential on the other hand.
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http://dx.doi.org/10.1039/c6sm00412aDOI Listing
May 2016

Complementary Molecular Dynamics and X-ray Reflectivity Study of an Imidazolium-Based Ionic Liquid at a Neutral Sapphire Interface.

J Phys Chem Lett 2015 Feb 26;6(3):549-55. Epub 2015 Jan 26.

†Institute for Theoretical Physics, FAU Erlangen-Nürnberg, Staudtstrasse 7, 91058 Erlangen, Germany.

Understanding the molecular-level behavior of ionic liquids (ILs) at IL-solid interfaces is of fundamental importance with respect to their application in, for example, electrochemical systems and electronic devices. Using a model system, consisting of an imidazolium-based IL ([C2Mim][NTf2]) in contact with a sapphire substrate, we have approached this problem using a complementary combination of high-resolution X-ray reflectivity measurements and atomistic molecular dynamics (MD) simulations. Our strategy enabled us to compare experimental and theoretically calculated reflectivities in a direct manner, thereby critically assessing the applicability of several force-field variants. On the other hand, using the best-matching MD description, we are able to describe the nature of the model IL-solid interface in appreciable detail. More specifically, we find that characteristic interactions between the surface hydroxyl groups and donor and acceptor sites on the IL constituents have a dominant role in inducing a multidimensional layering profile of the cations and anions.
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http://dx.doi.org/10.1021/jz5024493DOI Listing
February 2015

Crowding of receptors induces ring-like adhesions in model membranes.

Biochim Biophys Acta 2015 Nov 28;1853(11 Pt B):2984-91. Epub 2015 May 28.

Institut für Theoretische Physik and Cluster of Excellence: Engineering of Advanced Materials, Friedrich Alexander Universität Erlangen-Nürnberg, 91052 Erlangen, Germany; Insitut Ruđer Bošković, 10000 Zagreb, Croatia. Electronic address:

The dynamics of formation of macromolecular structures in adherent membranes is a key to a number of cellular processes. However, the interplay between protein reaction kinetics, diffusion and the morphology of the growing domains, governed by membrane mediated interactions, is still poorly understood. Here we show, experimentally and in simulations, that a rich phase diagram emerges from the competition between binding, cooperativity, molecular crowding and membrane spreading. In the cellular context, the spontaneously-occurring organization of adhesion domains in ring-like morphologies is particularly interesting. These are stabilized by the crowding of bulky proteins, and the membrane-transmitted correlations between bonds. Depending on the density of the receptors, this phase may be circumvented, and instead, the adhesions may grow homogeneously in the contact zone between two membranes. If the development of adhesion occurs simultaneously with membrane spreading, much higher accumulation of binders can be achieved depending on the velocity of spreading. The mechanisms identified here, in the context of our mimetic model, may shed light on the structuring of adhesions in the contact zones between two living cells. This article is part of a Special Issue entitled: Mechanobiology.
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http://dx.doi.org/10.1016/j.bbamcr.2015.05.025DOI Listing
November 2015

Forces and shapes as determinants of micro-swimming: effect on synchronisation and the utilisation of drag.

Soft Matter 2015 Mar;11(12):2364-71

Institute for Theoretical Physics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.

In this analytical study we demonstrate the richness of behaviour exhibited by bead-spring micro-swimmers, both in terms of known yet not fully explained effects such as synchronisation, and hitherto undiscovered phenomena such as the existence of two transport regimes where the swimmer shape has fundamentally different effects on the velocity. For this purpose we employ a micro-swimmer model composed of three arbitrarily-shaped rigid beads connected linearly by two springs. By analysing this swimmer in terms of the forces on the different beads, we determine the optimal kinematic parameters for sinusoidal driving, and also explain the pusher/puller nature of the swimmer. Moreover, we show that the phase difference between the swimmer's arms automatically attains values which maximise the swimming speed for a large region of the parameter space. Apart from this, we determine precisely the optimal bead shapes that maximise the velocity when the beads are constrained to be ellipsoids of a constant volume or surface area. On doing so, we discover the surprising existence of the aforementioned transport regimes in micro-swimming, where the motion is dominated by either a reduction of the drag force opposing the beads, or by the hydrodynamic interaction amongst them. Under some conditions, these regimes lead to counter-intuitive effects such as the most streamlined shapes forming locally the slowest swimmers.
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http://dx.doi.org/10.1039/c4sm02611jDOI Listing
March 2015

Association rates of membrane-coupled cell adhesion molecules.

Biophys J 2014 Dec 2;107(11):L33-6. Epub 2014 Dec 2.

Institut für Theoretische Physik and Cluster of Excellence Engineering of Advanced Materials, Friedrich-Alexander-Universität, Erlangen, Germany; Institute Ruđer Bošković, Division of Physical Chemistry, Zagreb, Croatia. Electronic address:

Thus far, understanding how the confined cellular environment affects the lifetime of bonds, as well as the extraction of complexation rates, has been a major challenge in studies of cell adhesion. Based on a theoretical description of the growth curves of adhesion domains, we present a new (to our knowledge) method to measure the association rate k(on) of ligand-receptor pairs incorporated into lipid membranes. As a proof of principle, we apply this method to several systems. We find that the k(on) for the interaction of biotin with neutravidin is larger than that for integrin binding to RGD or sialyl Lewis(x) to E-selectin. Furthermore, we find k(on) to be enhanced by membrane fluctuations that increase the probability for encounters between the binders. The opposite effect on k(on) could be attributed to the presence of repulsive polymers that mimic the glycocalyx, which points to two potential mechanisms for controlling the speed of protein complexation during the cell recognition process.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255260PMC
http://dx.doi.org/10.1016/j.bpj.2014.10.033DOI Listing
December 2014

Establishing conditions for simulating hydrophobic solutes in electric fields by molecular dynamics: effects of the long-range van der Waals treatment on the apparent particle mobility.

J Mol Model 2014 Aug 8;20(8):2359. Epub 2014 Aug 8.

Cluster of Excellence: Engineering of Advanced Materials, Friedrich-Alexander University Erlangen-Nuremberg, Nägelsbachstraße 49b, 91052, Erlangen, Germany.

Despite considerable effort over the last decade, the interactions between solutes and solvents in the presence of electric fields have not yet been fully understood. A very useful manner in which to study these systems is through the application of molecular dynamics (MD) simulations. However, a number of MD studies have shown a tremendous sensitivity of the migration rate of a hydrophobic solute to the treatment of the long range part of the van der Waals interactions. While the origin of this sensitivity was never explained, the mobility is currently regarded as an artifact of an improper simulation setup. We explain the spread in observed mobilites by performing extensive molecular dynamics simulations using the GROMACS software package on a system consisting of a model hydrophobic object (Lennard-Jones particle) immersed in water both in the presence and absence of a static electric field. We retrieve a unidirectional field-induced mobility of the hydrophobic object when the forces are simply truncated. Careful analysis of the data shows that, only in the specific case of truncated forces, a non-zero van der Waals force acts, on average, on the Lennard-Jones particle. Using the Stokes law we demonstrate that this force yields quantitative agreement with the field-induced mobility found within this setup. In contrast, when the treatment of forces is continuous, no net force is observed. In this manner, we provide a simple explanation for the previously controversial reports.
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http://dx.doi.org/10.1007/s00894-014-2359-5DOI Listing
August 2014