TY - JOUR A1 - Javanainen, Matti A1 - Martinez-Seara, Hector A1 - Metzler, Ralf A1 - Vattulainen, Ilpo T1 - Diffusion of Integral Membrane Proteins in Protein-Rich Membranes JF - The journal of physical chemistry letters N2 - The lateral diffusion of embedded proteins along lipid membranes in protein-poor conditions has been successfully described in terms of the Saffman-Delbruck (SD) model, which predicts that the protein diffusion coefficient D is weakly dependent on its radius R as D proportional to ln(1/R). However, instead of being protein-poor, native cell membranes are extremely crowded with proteins. On the basis of extensive molecular simulations, we here demonstrate that protein crowding of the membrane at physiological levels leads to deviations from the SD relation and to the emergence of a stronger Stokes-like dependence D proportional to 1/R. We propose that this 1/R law mainly arises due to geometrical factors: smaller proteins are able to avoid confinement effects much better than their larger counterparts. The results highlight that the lateral dynamics in the crowded setting found in native membranes is radically different from protein-poor conditions and plays a significant role in formation of functional multiprotein complexes. Y1 - 2017 U6 - https://doi.org/10.1021/acs.jpclett.7b01758 SN - 1948-7185 VL - 8 SP - 4308 EP - 4313 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Palyulin, Vladimir V. A1 - Mantsevich, Vladimir N. A1 - Klages, Rainer A1 - Metzler, Ralf A1 - Chechkin, Aleksei V. T1 - Comparison of pure and combined search strategies for single and multiple targets JF - The European physical journal : B, Condensed matter and complex systems N2 - We address the generic problem of random search for a point-like target on a line. Using the measures of search reliability and efficiency to quantify the random search quality, we compare Brownian search with Levy search based on long-tailed jump length distributions. We then compare these results with a search process combined of two different long-tailed jump length distributions. Moreover, we study the case of multiple targets located by a Levy searcher. Y1 - 2017 U6 - https://doi.org/10.1140/epjb/e2017-80372-4 SN - 1434-6028 SN - 1434-6036 VL - 90 SP - 20 EP - 37 PB - Springer CY - New York ER - TY - JOUR A1 - Caetano, Daniel L. Z. A1 - de Carvalho, Sidney J. A1 - Metzler, Ralf A1 - Cherstvy, Andrey G. T1 - Critical adsorption of periodic and random polyampholytes onto charged surfaces JF - Physical chemistry, chemical physics : a journal of European Chemical Societies N2 - How different are the properties of critical adsorption of polyampholytes and polyelectrolytes onto charged surfaces? How important are the details of polyampholyte charge distribution on the onset of critical adsorption transition? What are the scaling relations governing the dependence of critical surface charge density on salt concentration in the surrounding solution? Here, we employ Metropolis Monte Carlo simulations and uncover the scaling relations for critical adsorption for quenched periodic and random charge distributions along the polyampholyte chains. We also evaluate and discuss the dependence of the adsorbed layer width on solution salinity and details of the charge distribution. We contrast our findings to the known results for polyelectrolyte adsorption onto oppositely charged surfaces, in particular, their dependence on electrolyte concentration. Y1 - 2017 U6 - https://doi.org/10.1039/c7cp04040g SN - 1463-9076 SN - 1463-9084 VL - 19 SP - 23397 EP - 23413 PB - Royal Society of Chemistry CY - Cambridge ER - TY - GEN A1 - Javanainen, Matti A1 - Martinez-Seara, Hector A1 - Metzler, Ralf A1 - Vattulainen, Ilpo Tapio T1 - Diffusion of Proteins and Lipids in Protein-Rich Membranesa T2 - Biophysical journal Y1 - 2018 U6 - https://doi.org/10.1016/j.bpj.2017.11.3009 SN - 0006-3495 SN - 1542-0086 VL - 114 IS - 3 SP - 551A EP - 551A PB - Cell Press CY - Cambridge ER - TY - GEN A1 - Gudowska-Nowak, Ewa A1 - Lindenberg, Katja A1 - Metzler, Ralf T1 - Preface: Marian Smoluchowski’s 1916 paper—a century of inspiration T2 - Journal of physics : A, Mathematical and theoretical Y1 - 2017 U6 - https://doi.org/10.1088/1751-8121/aa8529 SN - 1751-8113 SN - 1751-8121 VL - 50 IS - 38 PB - IOP Publ. Ltd. CY - Bristol ER - TY - JOUR A1 - Norregaard, Kamilla A1 - Metzler, Ralf A1 - Ritter, Christine M. A1 - Berg-Sorensen, Kirstine A1 - Oddershede, Lene Broeng T1 - Manipulation and Motion of Organelles and Single Molecules in Living Cells JF - Chemical reviews N2 - The biomolecule is among the most important building blocks of biological systems, and a full understanding of its function forms the scaffold for describing the mechanisms of higher order structures as organelles and cells. Force is a fundamental regulatory mechanism of biomolecular interactions driving many cellular processes. The forces on a molecular scale are exactly in the range that can be manipulated and probed with single molecule force spectroscopy. The natural environment of a biomolecule is inside a living cell, hence, this is the most relevant environment for probing their function. In vivo studies are, however, challenged by the complexity of the cell. In this review, we start with presenting relevant theoretical tools for analyzing single molecule data obtained in intracellular environments followed by a description of state-of-the art visualization techniques. The most commonly used force spectroscopy techniques, namely optical tweezers, magnetic tweezers, and atomic force microscopy, are described in detail, and their strength and limitations related to in vivo experiments are discussed. Finally, recent exciting discoveries within the field of in vivo manipulation and dynamics of single molecule and organelles are reviewed. Y1 - 2017 U6 - https://doi.org/10.1021/acs.chemrev.6b00638 SN - 0009-2665 SN - 1520-6890 VL - 117 IS - 5 SP - 4342 EP - 4375 PB - American Chemical Society CY - Washington ER - TY - GEN A1 - Metzler, Ralf T1 - Gaussianity Fair BT - the Riddle of Anomalous yet Non-Gaussian Diffusion T2 - Biophysical journal Y1 - 2017 U6 - https://doi.org/10.1016/j.bpj.2016.12.019 SN - 0006-3495 SN - 1542-0086 VL - 112 IS - 3 SP - 413 EP - 415 PB - Cell Press CY - Cambridge ER - TY - GEN A1 - Metzler, Ralf T1 - Anomalous Diffusion in Membranes and the Cytoplasm of Biological Cells T2 - Biophysical journal Y1 - 2017 U6 - https://doi.org/10.1016/j.bpj.2016.11.2577 SN - 0006-3495 SN - 1542-0086 VL - 112 IS - 3 SP - 476A EP - 476A PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Liu, Lin A1 - Cherstvy, Andrey G. A1 - Metzler, Ralf T1 - Facilitated Diffusion of Transcription Factor Proteins with Anomalous Bulk Diffusion JF - The journal of physical chemistry : B, Condensed matter, materials, surfaces, interfaces & biophysical chemistry N2 - What are the physical laws of the diffusive search of proteins for their specific binding sites on DNA in the presence of the macromolecular crowding in cells? We performed extensive computer simulations to elucidate the protein target search on DNA. The novel feature is the viscoelastic non-Brownian protein bulk diffusion recently observed experimentally. We examine the influence of the protein-DNA binding affinity and the anomalous diffusion exponent on the target search time. In all cases an optimal search time is found. The relative contribution of intermittent three-dimensional bulk diffusion and one-dimensional sliding of proteins along the DNA is quantified. Our results are discussed in the light of recent single molecule tracking experiments, aiming at a better understanding of the influence of anomalous kinetics of proteins on the facilitated diffusion mechanism. Y1 - 2017 U6 - https://doi.org/10.1021/acs.jpcb.6b12413 SN - 1520-6106 VL - 121 SP - 1284 EP - 1289 PB - American Chemical Society CY - Washington ER - TY - JOUR A1 - Godec, Aljaž A1 - Metzler, Ralf T1 - First passage time statistics for two-channel diffusion JF - Journal of physics : A, Mathematical and theoretical N2 - We present rigorous results for the mean first passage time and first passage time statistics for two-channel Markov additive diffusion in a 3-dimensional spherical domain. Inspired by biophysical examples we assume that the particle can only recognise the target in one of the modes, which is shown to effect a non-trivial first passage behaviour. We also address the scenario of intermittent immobilisation. In both cases we prove that despite the perfectly non-recurrent motion of two-channel Markov additive diffusion in 3 dimensions the first passage statistics at long times do not display Poisson-like behaviour if none of the phases has a vanishing diffusion coefficient. This stands in stark contrast to the standard (one-channel) Markov diffusion counterpart. We also discuss the relevance of our results in the context of cellular signalling. KW - first passage time KW - Markov additive processes KW - Fokker-Planck equation KW - random search processes KW - coupled initial boundary value problem KW - cellular signalling KW - asymptotic analysis Y1 - 2017 U6 - https://doi.org/10.1088/1751-8121/aa5204 SN - 1751-8113 SN - 1751-8121 VL - 50 IS - 8 PB - IOP Publ. Ltd. CY - Bristol ER -