PubMed_ArguminSci  

PubMed:23912807 JSONTXT 7 Projects

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Id Subject Object Predicate Lexical cue
T1 100-328 DRI_Background denotes More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to.
T2 329-689 DRI_Background denotes While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour.
T3 773-967 DRI_Background denotes Furthermore, biological macromolecules live and operate in an extremely structured and complex environment within the cell (endoplasmic reticulum, Golgi apparatus, cytoskeletal structures, etc).
T4 968-1116 DRI_Approach denotes Hence, to further complicate the picture, the interior of the cell is by no means a simply crowded medium, rather, a most crowded and confining one.
T5 1117-1426 DRI_Background denotes In recent times, several approaches have been developed in the attempt to take into account important factors such as the ones mentioned above, at both theoretical and experimental levels, so that this field of research is now emerging as one of the most thriving in molecular and cell biology (see figure 1).
T6 1611-1719 DRI_Background denotes The arrow flags the 2003 'EMBO Workshop on Biological Implications of Macromolecular Crowding' (Embo, 2012).
T7 1720-1887 DRI_Approach denotes Right: number of citations to articles containing the word 'crowding' limited to the same domains (bars) and an exponential regression curve (source: Elsevier Scopus).
T8 1888-2147 DRI_Background denotes To promote the importance of molecular crowding and confinement and provide researchers active in this field an interdisciplinary forum for meeting and exchanging ideas, we recently organized an international conference held in Ascona from 10 to 14 June 2012.
T9 2539-2685 DRI_Background denotes The meeting was intended and has been organized to bring theoreticians and experimentalists together in the attempt to promote an active dialogue.
T10 2686-2895 DRI_Outcome denotes Moreover, we wanted different disciplines to be represented, notably physics and chemistry, besides biology, as cross-fertilization is proving an increasingly fundamental source of inspiration and advancement.
T11 3061-3270 DRI_Background denotes PB, one of the scientific journals of the Institute of Physics (IOP), is one of the most dynamic and lively forums active at the interface between biology on one side, and physics and mathematics on the other.
T12 3271-3470 DRI_Background denotes As its mission is stated by IOP, PB 'focuses on research in which physics-based approaches lead to new insights into biological systems at all scales of space and time, and all levels of complexity'.
T13 3471-3663 DRI_Background denotes For these reasons, and also in view of its high reputation and broad readership, PB appears to be the ideal place for disseminating the thriving pieces of research presented at the conference.
T14 3664-3813 DRI_Approach denotes We are extremely grateful to PB and its kind and efficient editorial staff who helped make this issue a great scientific follow-up to the conference.
T15 3814-4007 DRI_Outcome denotes The opening lecture of the conference, the first of four day-opening keynote lectures, was given by Allen P Minton from NIH (USA), possibly the most influential among the pioneers in the field.
T16 4169-4286 DRI_Challenge denotes It is clear that the concept of excluded volume as a key factor remains central to the concept of molecular crowding.
T17 4287-4485 DRI_Background denotes As a consequence, simple descriptive paradigms borrowed essentially from colloid physics may still provide useful tools to understand the subtle effects of crowding and confinement in living matter.
T18 4486-4676 DRI_Outcome denotes The contiguity between crowding, colloids and soft matter further emerged as an important concept in the course of the conference in several theoretical lectures and a few experimental ones.
T19 5008-5146 DRI_Background denotes In particular, he showed the importance of the shape of crowding particles in affecting folding oligomerization of amyloidogenic peptides.
T20 5147-5370 DRI_Background denotes Johannes Schöneberg, from IMPRS, Mathematics Institute (Germany), illustrated ReaDDy , a newly developed particle-based simulation software tool for reaction-diffusion dynamics, developed in the group of Frank Noe at EMPRS.
T21 5371-5579 DRI_Challenge denotes He showed that ReaDDy makes it possible to bridge the gap between soft matter and molecular dynamics (MD) simulations on the one hand and particle-based stochastic reaction-diffusion simulations on the other.
T22 5742-5888 DRI_Background denotes The tutorial session was indeed successful and the broad possibilities offered by the simulation toolkit appeared to be clear to the participants.
T23 6095-6362 DRI_Outcome denotes Starting from a modification of the well-known Smoluchowski approach to calculate the encounter rate of diffusion-limited reactions, he showed how more realistic situations accounting for crowding effects could be treated equally well on the same theoretical grounds.
T24 6363-6608 DRI_Outcome denotes This talk marked an important point in the conference as it reinforced the idea that simple models of theoretical physics still have the power to provide inspiring results in spite of the intrinsic simplifications of such theoretical approaches.
T25 6609-6816 DRI_Approach denotes Along the same lines, Nicolas Dorsaz, from the University of Cambridge (UK), proposed an extension of the Smoluchowski framework that incorporates repulsive and attracting interactions between the reactants.
T26 6817-6948 DRI_Background denotes This approach was illustrated by reaction rates obtained from event-driven Brownian dynamics and dynamical Monte Carlo simulations.
T27 6949-7125 DRI_Background denotes Another striking example of the physical subtleties associated with modelling crowding effects was provided by Jeffrey Skolnick, from the Georgia Institute of Technology (USA).
T28 7126-7254 DRI_Background denotes He examined the role of hydrodynamic interactions in the self-organization of biological assemblies in the presence of crowding.
T29 7255-7487 DRI_Challenge denotes His results strongly suggest that hydrodynamic interactions greatly affect the kinetics of self-assembly reactions, so that including them in the picture appears crucial for understanding the dynamics of biological systems in vivo .
T30 7488-7788 DRI_Outcome denotes Margareth Cheung, from the University of Houston (USA), emphasized that how the crowded environment inside a cell affects the structural conformation of a protein with a spherical shape is a vital question because the geometry of proteins and protein-protein complexes are far from globules in vivo .
T31 7789-7960 DRI_Challenge denotes Her work demonstrates the malleability of 'native' proteins and implies that crowding-induced shape changes may be important for protein function and malfunction in vivo .
T32 7961-8109 DRI_Approach denotes Huan-Xiang Zhou, from the Florida State University (USA), focused on atomistic simulations of protein folding and binding under crowding conditions.
T33 8110-8258 DRI_Background denotes His lab has developed a post-processing method that allows the atomistic representation of proteins in folding and binding processes under crowding.
T34 8318-8445 DRI_Outcome denotes Other lecturers pointed out that there are still aspects not entirely explored in the effects of both crowding and confinement.
T35 8446-8689 DRI_Approach denotes As suggested in the talk by Gary Pielak, from the University of North Carolina (USA), the currently used synthetic crowding agents are far from being satisfactory in replicating naturally occurring effects associated with crowded environments.
T36 8690-8863 DRI_Challenge denotes For example, non-specific binding seems to play a subtle role in the cell, as natural macromolecules can induce both stabilization and destabilization when used as crowders.
T37 8864-8971 DRI_Challenge denotes It is indeed possible to fine-tune the effect of proteins, as crowders, on the stability of other proteins.
T38 8972-9144 DRI_Challenge denotes Another aspect that became clear is that new, more powerful methods need to be developed to study the effect of crowding, but even more to compare crowding and confinement.
T39 9145-9190 DRI_Outcome denotes Indeed, it appeared clear from the lecture by
T40 9209-9435 DRI_Outcome denotes , from the University of Naples (Italy), that a reliable comparison of the effects of crowding and confinement on the stability of proteins can only be based on the measurement of the whole stability curve of the same protein.
T41 9436-9581 DRI_Background denotes Controversial aspects do not pertain only to the influence of crowding on protein stability, but also to aggregation phenomena in natural fluids.
T42 9582-9708 DRI_Background denotes Domenico Sanfelice, from NIMR (London, UK), reported an interesting case of the apparent influence of crowding on aggregation.
T43 9709-9897 DRI_Challenge denotes Hen egg white, a possible natural medium to study macromolecules in crowded conditions can dramatically increase the aggregation kinetics of proteins with an inbuilt tendency to associate.
T44 9898-10101 DRI_Outcome denotes By carefully dissecting the phenomenology, it was shown that only part of this effect is due to crowding, while another factor playing an important role is the interaction with proteins from the milieu .
T45 10102-10207 DRI_Outcome denotes In other words, high-molecular-weight glycoproteins can act as efficient molecular seeds for aggregation.
T46 10208-10323 DRI_Background denotes A special topic of great relevance in the conference appeared to be the direct study of crowding in living systems.
T47 10629-10793 DRI_Background denotes In his keynote lecture, Dr Verkman led us on a wide and compelling tour, exploring the main experimental approaches to study molecular crowding in and around cells.
T48 10794-11405 DRI_Background denotes After a thorough examination of methods such as fluorescence recovery after photo-bleaching, fluorescence correlation spectroscopy, photo-activation localization microscopy and stochastic reconstruction microscopy, he concluded that the general consensus emerging from experimental studies is that the notion of universally anomalous diffusion in and around cells as a consequence of molecular crowding may not be correct, and that the slowing of diffusion in cells is less marked than has been widely assumed and can be simply described through a five- to sixfold reduction of the normal diffusion coefficient.
T49 11406-11667 DRI_Challenge denotes A Soranno, from the University of Zürich (Switzerland), described how, by employing FRET measurements, it is possible to quantify the effect of molecular crowding on the dimensions of the highly charged, intrinsically disordered protein human prothymosin alpha.
T50 11668-11852 DRI_Background denotes For a large variety of polymeric crowders (PEG, PVP, Ficoll, Dextran, PVA, PAA), a collapse of the polypeptide chain is observed with increasing polymer size and polymer concentration.
T51 11853-12004 DRI_Challenge denotes The largest extent of collapse is observed for polymer radii comparable to the dimensions of the protein, in agreement with theoretical considerations.
T52 12257-12372 DRI_Background denotes These are non-membrane-bound macromolecular assemblies that form from the dynamic interactions of RNA and proteins.
T53 12373-12564 DRI_Outcome denotes The assembly of RNP bodies may sensitively depend on the biophysical features of the surrounding cytoplasm, including the degree of crowding, transport coefficients and mechanical properties.
T54 12565-12725 DRI_Challenge denotes This dependency may have important implications for the RNA processing reactions involved in fundamental biological processes such as developmental cell growth.
T55 12726-13034 DRI_Outcome denotes Remarkably, Brangwynne showed how RNPs behave in the cell as liquid droplets, pointing to a possible entirely new means that the cell could use to control and fine-tune its internal processes, in fact, more than that, a completely unexplored, new state of organization of living matter, and a functional one.
T56 13035-13238 DRI_Approach denotes Giuseppe Zaccai, from Institut Laue Langevin, Grenoble (France), showed that protein dynamics is more sensitive than structure to environmental factors such as crowding, solvent, temperature or pressure.
T57 13239-13379 DRI_Outcome denotes Furthermore, he convincingly explained how neutron scattering provides unique experimental data to underpin MD calculations in this context.
T58 13380-13621 DRI_Approach denotes Following up on environment-induced modulations of protein functional dynamics, Ruth Nussinov, from Tel Aviv University (Israel), addressed the important problem of whether cellular signals can travel long distances in a crowded environment.
T59 13622-13910 DRI_Approach denotes She proposed a model based on the evolution of at least three properties: a modular functional organization of the cellular network, sequences in some key regions of proteins, such as linkers or loops, and compact interactions between proteins, possibly favoured by a crowded environment.
T60 14015-14126 DRI_Background denotes Lehn, 1987 Nobel Laureate in chemistry, offered a 'supramolecular view' of the field of molecular interactions.
T61 14127-14218 DRI_Background denotes Supramolecular chemistry explores the design of systems undergoing self-organization , i.e.
T62 14219-14390 DRI_Background denotes systems capable of generating well-defined functional supramolecular architectures by self-assembling from their components, thus behaving as programmed chemical systems .
T63 14391-14485 DRI_Background denotes Chemistry may therefore be considered an information science , the science of informed matter.
T64 14486-14737 DRI_Background denotes Supramolecular chemistry is intrinsically a dynamic chemistry in view of the ability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents.
T65 14738-14968 DRI_Approach denotes The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibly, so as to allow a continuous change in constitution by the reorganization and exchange of building blocks.
T66 14969-15080 DRI_Approach denotes These features define a constitutional dynamic chemistry (CDC) on both the molecular and supramolecular levels.
T67 15081-15244 DRI_Challenge denotes CDC takes advantage of dynamic constitutional diversity to allow variation and selection in response to either internal or external factors to achieve adaptation .
T68 15245-15438 DRI_Challenge denotes The merging of the features-information and programmability, dynamics and reversibility, constitution and structural diversity-points towards the emergence of adaptive and evolutive chemistry .
T69 15439-15534 DRI_Approach denotes The whole workshop could have not taken place without the help of the Centro Stefano Franscini.
T70 15535-15683 DRI_Background denotes The CSF is the congress centre of the Swiss Federal Institute of Technology of Zurich (ETH Zurich) and has been situated at Monte Verità since 1989.
T71 15684-15856 DRI_Challenge denotes It is an ideal meeting point for all members of the international scientific community who wish to discuss the state-of-the-art and new challenges of any field of research.
T72 15857-15969 DRI_Approach denotes The CSF supports 20-25 international conferences every year and, since 2010, up to ten winter doctoral schools1.
T73 15970-16099 DRI_Background denotes The competence and professionalism of the staff were at the same level of beauty and inspiring character as that of Monte Verità.
T74 16100-16257 DRI_Challenge denotes A meeting of this sort, if successful, leaves the audience with more open questions than settled answers, and this was definitely the case for Crowding 2012.
T75 16258-16422 DRI_Challenge denotes Excluded volume is clearly a fundamental concept that has allowed crowding, a very familiar concept in soft matter, to enter into the domain of biological sciences.
T76 16423-16508 DRI_Outcome denotes However, the complexity of the biological milieu calls for more refined descriptions.
T77 16624-16769 DRI_Approach denotes To what extent does the strong spatial inhomogeneity (clustering of molecules, cellular compartmentalization, etc) have to be taken into account?
T78 16876-17012 DRI_Approach denotes How does the diffusion proceed (diffusion, slow diffusion, sub-diffusion) given that the experimental evidences are still controversial?
T79 17013-17137 DRI_Outcome denotes In conclusion, we knew that allowing scientists with very different backgrounds and ideas to mingle was a hazardous attempt.
T80 17138-17281 DRI_Challenge denotes Despite that, the workshop turned out to be a very successful experiment, which was highly enjoyed both by the participants and the organizers.
T81 17282-17506 DRI_Background denotes Discussions sparked regularly among ever-changing groups, comprising senior scientists and students, despite the rather tight schedule, adding to the sense of fulfilment ignited by the outstanding level of the presentations.
T82 17507-17708 DRI_Outcome denotes Given the success of the meeting Crowding 2012, a new event has been organized and will take place on the same themes during fall 2013, this time in the beautiful scenery of the Loire valley in France.
T83 17709-17870 DRI_Background denotes The workshop 'Macromolecular crowding effects in cell biology: models and experiments' will be held on the CNRS campus in Orléans, France, on 24-25 October 2013.
T84 17871-17964 DRI_Approach denotes More information can be found on the workshop website: http://dirac.cnrs-orleans.fr/∼piazza/.