We report the experimental demonstration of tunable optical delay using carrier induced exciton dephasing in a GaAs quantum well. Fractional delays exceeding 200% have been obtained for an 8 ps optical pulse.
Abstract Amyloid-beta peptide (Aβ) is the primary component of water-insoluble extracellular plaques, one of the critical hallmarks of Alzheimer's disease (AD). Matrix metalloproteases (MMPs) are broad-spectrum proteases with diverse functions, including interactions with Aβ. Here we report single molecule measurements of MMP1 dynamics on Aβ-induced aggregates by calculating Forster Resonance Energy Transfer (FRET) between two dyes attached to the catalytic and hemopexin domains. We show that the two domains of MMP1 prefer closed conformations on Aβ-induced aggregates, in contrast to the preference for open conformations on collagen fibril, fibrin, and alpha-synuclein aggregates. We approximated the MMP1 dynamics by a two-state Poisson process and determined the kinetic rates of interconversion between the two states from histograms and correlations of FRET values. We performed molecular docking of MMP1 with Aβ using ClusPro, simulated MMP1 dynamics using different docking poses, and matched the experimental and simulated interdomain dynamics to identify an appropriate pose. We used simulations to create a two-dimensional map of correlations between every pair of MMP1 residues, which shows allosteric communications between the two MMP1 domains. We calculated a Gray Level Co-occurrence Matrix from the two-dimensional map of correlations and quantified MMP1 fluctuations by Shannon entropy. We identified the allosteric residues in the hemopexin domain by identifying residues having strong correlations with the catalytic motif residues. We identified that the residues I364, G369, P409, G410, and D418 in MMP1 have Aβ-specific allosteric correlations with the MMP1 catalytic motif by comparing residues for free and Aβ-bound MMP1. We used these Aβ-specific allosteric residues to select small molecule ligands after the virtual screening of molecules against Aβ-bound MMP1. Molecular understanding of interactions between MMP1 and Aβ-induced aggregates and identification of substrate-specific allosteric residues may enable controlling MMP1 function selectively on Aβ.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAssignment of secondary amide nitrogen-15 resonances of bleomycin A2 by two-dimensional multiple-quantum proton-nitrogen-15 shift-correlation NMR spectroscopySusanta K. Sarkar and Jerry D. GlicksonCite this: J. Am. Chem. Soc. 1986, 108, 21, 6814–6816Publication Date (Print):October 1, 1986Publication History Published online1 May 2002Published inissue 1 October 1986https://pubs.acs.org/doi/10.1021/ja00281a065https://doi.org/10.1021/ja00281a065research-articleACS PublicationsRequest reuse permissionsArticle Views48Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Fluorescent nanodiamonds (FNDs) emit in the near-IR and do not photobleach or photoblink. These properties make FNDs better suited for numerous imaging applications compared with commonly used fluorescence agents such as organic dyes and quantum dots. However, nanodiamonds do not form stable suspensions in aqueous buffer, are prone to aggregation, and are difficult to functionalize. Here we present a method for encapsulating nanodiamonds with silica using an innovative liposome-based encapsulation process that renders the particle surface biocompatible, stable, and readily functionalized through routine linking chemistries. Furthermore, the method selects for a desired particle size and produces a monodisperse agent. We attached biotin to the silica-coated FNDs and tracked the three-dimensional motion of a biotinylated FND tethered by a single DNA molecule with high spatial and temporal resolution.
Abstract Alpha-synuclein (aSyn) has implications in pathological protein aggregations in neurodegeneration. Matrix metalloproteases (MMPs) are broad-spectrum proteases and cleave aSyn, leading to aggregation. Previous reports showed that allosteric communications between the two domains of MMP1 on collagen fibril and fibrin depend on substrates, activity, and ligands. This paper reports quantification of allostery using single molecule measurements of MMP1 dynamics on aSyn-induced aggregates by calculating Forster Resonance Energy Transfer (FRET) between two dyes attached to the catalytic and hemopexin domains of MMP1. The two domains of MMP1 prefer open conformations that are inhibited by a single point mutation E219Q of MMP1 and tetracycline, an MMP inhibitor. A two-state Poisson process describes the interdomain dynamics, where the two states and kinetic rates of interconversion between them are obtained from histograms and autocorrelations of FRET values. Since a crystal structure of aSyn-bound MMP1 is unavailable, binding poses were predicted by molecular docking of MMP1 with aSyn using ClusPro. MMP1 dynamics were simulated using predicted binding poses and compared with the experimental interdomain dynamics to identify an appropriate pose. The selected aSyn-MMP1 binding pose near aSyn residue K45 was simulated and analyzed to define conformational changes at the catalytic site. Allosteric residues in aSyn-bound MMP1 exhibiting strong correlations with the catalytic motif residues were compared with allosteric residues in free MMP1, and aSyn-specific residues were identified. The allosteric residues in aSyn-bound MMP1 are K281, T283, G292, G327, L328, E329, R337, F343, G345, N346, Y348, G353, Q354, D363, Y365, S366, S367, F368, P371, R372, V374, K375, A379, F391, A394, R399, M414, F419, V426, and C466. Shannon entropy was defined to quantify MMP1 dynamics. Virtual screening was performed against a site on selected aSyn-MMP1 binding poses, which showed that lead molecules differ between free MMP1 and substrate-bound MMP1. Also, identifying aSyn-specific allosteric residues in MMP1 enabled further selection of lead molecules. In other words, virtual screening needs to take substrates into account for potential substrate-specific control of MMP1 activity in the future. Molecular understanding of interactions between MMP1 and aSyn-induced aggregates may open up the possibility of degrading aggregates by targeting MMPs.
The arrow of time is an irreversible phenomenon for a system of particles undergoing reversible dynamics. Since the time of Boltzmann to this day, the arrow of time has led to debate and research. However, the enormous growth of nanotechnology and associated experimental techniques has brought the arrow of time at the forefront because of its practical implications. Using simulations of one-dimensional diffusion of a system of particles, we show that the arrow of time is an emergent property of a large system. We show that the recurrence time for a system of particles to return to its original configuration grows rapidly as the number of particles grows. Based on the simulations, we have provided the expressions for recurrence times for classical particles, Fermions, and Bosons. A system of Bosons has the shortest recurrence time, whereas a system of classical particles has the longest recurrence time. The underlying distribution around the mean recurrence time is Poisson-distributed for Bosons and Gaussian-distributed for Fermions and classical particles. The probabilistic approach to encode dynamics enables testing processes other than diffusion and quantify their effects on the recurrence time.
Type IIA topoisomerases modify DNA topology by passing one segment of duplex DNA (transfer or T–segment) through a transient double-strand break in a second segment of DNA (gate or G–segment) in an ATP-dependent reaction. Type IIA topoisomerases decatenate, unknot and relax supercoiled DNA to levels below equilibrium, resulting in global topology simplification. The mechanism underlying this non-equilibrium topology simplification remains speculative. The bend angle model postulates that non-equilibrium topology simplification scales with the bend angle imposed on the G–segment DNA by the binding of a type IIA topoisomerase. To test this bend angle model, we used atomic force microscopy and single-molecule Förster resonance energy transfer to measure the extent of bending imposed on DNA by three type IIA topoisomerases that span the range of topology simplification activity. We found that Escherichia coli topoisomerase IV, yeast topoisomerase II and human topoisomerase IIα each bend DNA to a similar degree. These data suggest that DNA bending is not the sole determinant of non-equilibrium topology simplification. Rather, they suggest a fundamental and conserved role for DNA bending in the enzymatic cycle of type IIA topoisomerases.
We report the experimental realization of a tunable optical delay by exploiting unique incoherent nonlinear optical processes in semiconductors. The tunable optical delay takes advantage of the strong Coulomb interactions between excitons and free carriers and uses optical injection of free carriers to broaden and bleach an exciton absorption resonance. Fractional delay exceeding 200% has been obtained for an 8 ps optical pulse propagating near the heavy-hole excitonic transition in a GaAs quantum well structure. Tunable optical delay based on optical injection of free carriers avoids strong absorption of the pump beam and is also robust against variations in the frequency of the pump beam.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)