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Topological transitions in fluid lipid membranes: activation energy and force fields
No full textTopological transitions of fluid lipid membranes are fundamental processes for cell life. For example, they are required for endo- and exocytosis or to enable neurotransmitters to cross the neural synapses. They are also of strong interest in medicine and in the pharmaceutical industry, e.g. for the development of antivirals
and drug delivery.
Fluid lipid membranes can be treated not only from a biochemical perspective but also from a mechanical one, using the classical Canham-Helfrich elastic free energy which successfully describes many aspects of membrane dynamics but rules out the possibility of dealing with topological transitions. In this thesis, I develop, numerically demonstrate, and use a new Ginzburg-Landau type of free energy that treats the membrane as a diffuse interface, with the further ability to naturally handle topological changes, allowing the whole, full-scale topological transition to be simulated without interruption. The free energy functional approaches the Canham-Helfrich one in the limit of small width-to-vesicle-extension ratio, even accounting for the Gaussian energy term, which plays a crucial role during topology changes due to the celebrated Gauss-Bonnet theorem. Coupled with a rare event technique, the method is also capable of computing the force fields needed to overcome the elastic energy barriers involved in the topological transformation.
Inspired by the idea that fusion and fission proteins could have evolved in nature in order to carry out a minimal work expenditure, I evaluate the minimal free energy pathway for the transition between two spherical large unilamellar vesicles and a dumbbell-shaped one. Results show merging intermediates reminiscent of those found in experiments and molecular dynamics simulations, while the obtained forces are in excellent agreement, in terms of intensity, scale, and spatial localization with experimental data on typical fission protein systems. As regards fusion, the obtained force field is extremely intense to be exerted by fusion proteins and its strong localization suggests that a local modification of the Gaussian modulus can substantially affect the pathway during the merging process. Therefore, I also investigate this scenario, showing that the energy barrier is drastically lowered and the pathway substantially changed by such a modification, and discuss biological examples in which it might be important. The case of vesicles with non-zero bilayer spontaneous curvature is considered as well. The ability of the diffuse interface to capture important features of the stalk-hemifusion pathway is revealed by considering the transition between a single oblate vesicle and a toroidal one, showing that a stabilization of the hemifusion-like intermediate occurs in accordance with the known fusogenic effect of lipids with negative (monolayer) spontaneous curvature. The same stabilization is obtained pushing the model toward its limits, namely dealing with small vesicles that start the merging process at closer distances. The lateral stress profile of the membrane diffuse interface is calculated as a function of the elastic rigidities, yielding a coarse-grained version of molecular model findings.
Additionally, the diffuse-interface approach is used to study the fission of lipid tubules. The obtained elastic picture is compatible with many features of dynamin-driven constriction, and allows to speculate on the mechanism that couples the polymerization length to the fission site position.
Finally, I discuss the extension of the model with a term that accounts for area-difference elasticity and introduce a possible way to deal with intermembrane interactions. Preliminary results on thermal fluctuations and coupling with macroscopic hydrodynamic motion are also shown
The diffuse interface description of fluid lipid membranes captures key features of the hemifusion pathway and lateral stress profile
Full text linkTopological transitions of lipid membranes are ubiquitous in key biological processes for cell life, like neurotransmission, fertilization, morphogenesis, and viral infections. Despite this, they are not well understood due to their multiscale nature, which limits the use of molecular models and calls for a mesoscopic approach such as the celebrated Canham-Helfrich one. Unfortunately, such a model cannot handle topological transitions, hiding the crucial involved forces and the appearance of the experimentally observed hemifused intermediates. In this work, we describe the membrane as a diffuse interface preserving the Canham-Helfrich elasticity. We show that pivotal features of the hemifusion pathway are captured by this mesoscopic approach, e.g. a (meta)stable hemifusion state and the fusogenic behavior of negative monolayer spontaneous curvatures. The membrane lateral stress profile is calculated as a function of the elastic rigidities, yielding a coarse-grained version of molecular models findings. Insights into the fusogenic mechanism are reported and discussed
Topological transitions in fluid lipid vesicles: activation energy and force fields
Full text linkLipid bilayer membranes are the fundamental biological barriers that permit
life.
The bilayer dynamics largely participates in orchestrating cellular workings
and is characterized by substantial stability together with extreme plasticity
that allows controlled morphological/topological changes.
Modeling and understanding the topological change of vesicle-like membrane at
the scale of a full cell has proved an elusive aim.
We propose and discuss here a continuum model able to encompass the
fusion/fission transition of a bilayer membrane at the scale of a Large
Unilamellar Vesicle and evaluate the minimal free energy path across the
transition, inspired by the idea that fusion/fission-inducing proteins have
evolved in Nature towards minimal work expenditure.
The results predict the correct height for the energetic barrier and provide
the force field that, by acting on the membrane, can induce the transition.
They are found in excellent agreement, in terms of intensity, scale, and
spatial localization with experimental data on typical protein systems at play
during the transition.
The model may pave the way for the development of more complete models of the
process where the dynamics is coupled to the fluid internal and external
environment and to other applications where the topological changes do either
occur or should be prevented
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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