Cytokinesis requires a apoptosis-linked gene 2 interacting protein X (ALIX) and a 55 kDa midbody centrosomal protein (CEP55) to activate the cell abscission in somatic cells. However, in germ cells, ...CEP55 forms intercellular bridges with testis-expressed gene 14 (TEX14), which blocks the cell abscission. These intercellular bridges play important roles in the synchronization of the germ cells and facilitate the coordinated passage of organelles and molecules between germ cells. If TEX14 is intentionally removed, intercellular bridges are disrupted, leading to sterility. Hence, a deeper understanding regarding the roles of TEX14 can provide significant insights into the inactivation of abscission and the inhibition of proliferation in cancer cells. Previous experimental studies have shown that the high affinity and low dissociation rate of TEX14 for CEP55 prevent ALIX from binding CEP55 and inactivate the germ cell abscission. However, detailed information about how TEX14 interacts with CEP55 to prevent the cell abscission is still lacking. To gain more specific insights into the interactions between CEP55 and TEX14 and the difference in reactivity between TEX14 and ALIX, we performed well-tempered metadynamics simulations of these protein complexes using atomistic models of CEP55, TEX14, and ALIX. We identified the major binding residues of TEX14 and ALIX with CEP55 by using 2D Gibbs free energy evaluations, the results of which are consistent with previous experimental studies. Our results may help design synthetic TEX14 mimicking peptides, which can bind CEP55 and facilitate the inactivation of abscission in abnormal cells, including cancer cells.
We performed molecular dynamics simulations of the systems consisting of C60 molecules and dipalmitoylphosphatidylcholine (DPPC) monolayer membranes to study the penetration of C60 into lung ...surfactant (LS) membranes. The potential of mean force of the C60 penetration through the LS membrane was calculated as a function of the distance of a C60 molecule from the DPPC monolayer membrane. The free energy minimum of around 43 kcal/mol is located in the DPPC tail region, indicating that the C60 molecules can accumulate in the LS membrane region. The energy decomposition shows the main driving force of the C60 accumulation in the lipid tail region is the van der Waals interaction with the hydrocarbon tails of DPPC lipids. Finally, we observed that the water evaporation rate can be significantly enhanced by the accumulation of C60 molecules in the membrane tail region.
We have performed coarse‐grained molecular dynamics simulations of organic photovoltaic (OPV) 5wcells consisting of poly(3‐hexyl‐thiophene) (P3HT), phenyl‐C61‐butyric acid methyl ester (PC61BM), and ...phenyl‐C71‐butyricacid methyl ester (PC71BM) to investigate the effects of the solvent evaporation rate and the number of components in the morphological stability of OPV. Two different solvent evaporation processes were employed in this study. In the instantaneous solvent removal process, unstable pores are formed because of the slow translational relaxation of the electron receptors. In case of the gradual solvent removal process, the stable film formation is observed without any pore. In addition, the ternary OPV system shows better stability than binary systems by slowing down the phase separation.
Morphological changes of three OPV systems upon instantaneous (left) and gradual (right) solvent removal processes.
A new type of bis‐PDA, in which two PDAs are linked via an intervening p‐phenylene group, is developed. The Bis‐PDA‐Ph displays exceptional thermochromic reversibility owing to the presence of unique ...hydrophobic interactions between alkyl chains as well as aryl moieties. The Bis‐PDA‐Ph has a well‐packed structure that causes it to display a clear blue to red colorimetric transition at elevated temperatures. To elucidate the molecular origin of the thermochromic response, a theoretical simulation of the new PDA, the results of which successfully explain the thermochromic reversibility phenomenon, is conducted. Furthermore, Bis‐PDA‐Ph‐embedded polymer fibers are used as a thermochromic sensor material. It displays excellent reversibility between 20–120 °C, which is the largest temperature range reported thus far for PDA based sensors. Finally, transient absorption spectroscopy is employed for the first time to analyze the temperature‐dependent fluorescence change of the new PDA.
The Bis‐PDA‐Ph (two PDAs are linked via an intervening p‐phenylene group) displays exceptional thermochromic reversibility with a blue to red colorimetric transition at elevated temperatures. To elucidate the molecular origin of the thermochromic response, a theoretical simulation of the new PDA which explains the reversibility phenomenon, is conducted. Furthermore, Bis‐PDA‐Ph‐embedded fibers display excellent reversibility between 20–120 °C.
To achieve endemic phases, repeated vaccinations are necessary. However, individuals may grapple with whether to get vaccinated due to potential side effects. When an individual is already immune due ...to previous infections or vaccinations, the perceived risk from vaccination is often less than the risk of infection. Yet, repeated rounds of vaccination can lead to avoidance, impeding the establishment of endemic phases. We explore this phenomenon using an individual-based Monte Carlo simulation, validating our findings with game theory. The Nash equilibrium encapsulates individuals' non-cooperative behavior, while the system's optimal value represents the societal benefits of altruistic cooperation. We define the difference between these as the price of anarchy. Our simulations reveal that the price of anarchy must fall below a threshold of 12.47 for endemic phases to be achieved in a steady state. This suggests that for a basic reproduction number of 10, a consistent vaccination rate greater than 89% is required. These findings offer new insights into vaccination-related decision-making and can inform effective strategies to tackle infectious diseases.
We have performed canonical ensemble Monte Carlo simulations of a primitive DNA model to study the conformation of 2.56 ~ 21.8 μm long DNA molecules confined in nanochannels at various ionic ...concentrations with the comparison of our previous experimental findings. In the model, the DNA molecule is represented as a chain of charged hard spheres connected by fixed bond length and the nanochannels as planar hard walls. System potentials consist of explicit electrostatic potential along with short-ranged hard-sphere and angle potentials. Our primitive model system provides valuable insight into the DNA conformation, which cannot be easily obtained from experiments or theories. First, the visualization and statistical analysis of DNA molecules in various channel dimensions and ionic strengths verified the formation of locally coiled structures such as backfolding or hairpin and their significance even in highly stretched states. Although the folding events mostly occur within the region of ~0.5 μm from both chain ends, significant portion of the events still take place in the middle region. Second, our study also showed that two controlling factors such as channel dimension and ionic strength widely used in stretching DNA molecules have different influence on the local DNA structure. Ionic strength changes local correlation between neighboring monomers by controlling the strength of electrostatic interaction (and thus the persistence length of DNA), which leads to more coiled local conformation. On the other hand, channel dimension controls the overall stretch by applying the geometric constraint to the non-local DNA conformation instead of directly affecting local correlation. Third, the molecular weight dependence of DNA stretch was observed especially in low stretch regime, which is mainly due to the fact that low stretch modes observed in short DNA molecules are not readily accessible to much longer DNA molecules, resulting in the increase in the stretch of longer DNA molecules.
Geometric factors affecting the enhanced electrocatalysis on nanoporous Pt (L2-ePt) were examined by electrochemical methods and computer simulations. The experimental results revealed that the ...electrochemical enhancement of O2 and H2O2 does not come only from expansion of the active surface area (so-called roughness factor, f R) of L2-ePt. The presence of extra contribution was verified by the fact that significant enhancement in electrocatalytic reactions remained even after the effect of the f R was eliminated from the electrochemical redox behavior of O2 and H2O2 on L2-ePt electrodes. Not only the voltammetric observation but also potentiometric pH responses of L2-ePt suggested the presence of unique nanoporous effects other than the surface enlargement in regard to heterogeneous electrochemical reactions. L2-ePt showed near Nernstian behavior, faster response time, and less hysteresis even if the real surface area was smaller than that of flat Pt. Increased residence time near the electrode surface due to extremely confined space of nanoporous structure was proposed as possible origins and examined by the Monte Carlo simulations of simple model electrodes. The theoretical approaches indicated that long residence time of reactant at electrode surface by confinement effect of the nanoporous environment well accounted for the experimental results.
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•Exchange rates of alkanethiolates in SAMs on gold were determined by MALDI-TOF MS.•For the study of self-exchange, a deuterated alkanethiol was designed and prepared.•It has the same ...molecular properties as the non-deuterated alkanethiol but a different molecular weight.•The influences of various conditions on exchange rates were accessed.
In this paper, we describe a new method for determining the exchange rates of alkanethiolates in self-assembled monolayers (SAMs) on gold using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze the compositions of the alkanethiolate in SAMs rapidly and directly. In particular, to investigate the self-exchange of alkanethiols, we prepared a deuterated alkanethiol that has the same molecular properties as the non-deuterated alkanethiol but a different molecular weight. SAMs consisting of deuterated alkanethiolates were immersed in a solution of the non-deuterated alkanethiol, and the influences of the immersion time, temperature, concentration, and solvent on the self-exchange rates were investigated. Furthermore, we assessed the exchange rates among alkanethiols with different carbon chain lengths and different size of ethylene glycol units. In addition, we performed molecular dynamics simulations using a model SAM system in order to understand the molecular mechanism of the exchange process.
Intercellular bridges are a conserved feature of spermatogenesis in mammalian germ cells and derive from arresting cell abscission at the final stage of cytokinesis. However, it remains to be fully ...understood how germ cell abscission is arrested in the presence of general cytokinesis components. The TEX14 (testis-expressed gene 14) protein is recruited to the midbody and plays a key role in the inactivation of germ cell abscission. To gain insights into the structural organization of TEX14 at the midbody, we have determined the crystal structures of the EABR endosomal sorting complex required for transport (ESCRT) and ALIX-binding region of CEP55 bound to the TEX14 peptide (or its chimeric peptides) and performed functional characterization of the CEP55–TEX14 interaction by multiexperiment analyses. We show that TEX14 interacts with CEP55-EABR via its AxGPPx₃Y (Ala793, Gly795, Pro796, Pro797, and Tyr801) and PP (Pro803 and Pro804) sequences, which together form the AxGPPx₃YxPP motif. TEX14 competitively binds to CEP55-EABR to prevent the recruitment of ALIX, which is a component of the ESCRT machinery with the AxGPPx₃Y motif. We also demonstrate that a high affinity and a low dissociation rate of TEX14 to CEP55, and an increase in the local concentration of TEX14, cooperatively prevent ALIX from recruiting ESCRT complexes to the midbody. The action mechanism of TEX14 suggests a scheme of how to inactivate the abscission of abnormal cells, including cancer cells.
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