Publications by authors named "Robert Briber"

20 Publications

  • Page 1 of 1

Extended delivery of cationic drugs from contact lenses loaded with unsaturated fatty acids.

Eur J Pharm Biopharm 2020 Oct 1;155:1-11. Epub 2020 Aug 1.

Lynthera Corporation, 1200 Corporate Blvd., STE 10C, Lancaster, PA 17601, United States. Electronic address:

This paper describes the use of surface-active anionic unsaturated fatty acids in commercial contact lenses to extend drug release duration and regulate delivery dosage. We studied the effect of oleic acid on the in vitro release kinetics of three cationic drugs, and two anionic drugs from silicone hydrogel contact lenses. The release duration of the cationic drugs: tetracaine hydrochloride, bupivacaine hydrochloride, and ketotifen fumarate was significantly extended from less than a day to more than a month because of the presence of oleic acid in the contact lenses. With a simple change in the fatty acid loading media, we could duplicate a similar efficacy by loading oleic acid in conventional non-silicone hydrogel contact lenses. The fitted effective diffusivity values of the three cationic drugs significantly decrease when the oleic acid weight % in the lenses is increased. By using two other unsaturated fatty acids, linoleic and α-linolenic acid, the release duration of ketotifen fumarate was also significantly extended in silicone hydrogel contact lenses. In contrast, the release of two anionic drugs, diclofenac sodium and flurbiprofen sodium, was accelerated for oleic acid modified lenses. These results show the dominating impact of coupling charge interactions between the drug and the fatty acid carrier molecules to precisely adjust delivery rate and dosage from a contact lens.
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http://dx.doi.org/10.1016/j.ejpb.2020.07.033DOI Listing
October 2020

Formation of Drug-Participating Catanionic Aggregates for Extended Delivery of Non-Steroidal Anti-Inflammatory Drugs from Contact Lenses.

Biomolecules 2019 10 10;9(10). Epub 2019 Oct 10.

Lynthera Corporation, 1200 Corporate Blvd., STE 10C, Lancaster, PA 17601, USA.

This paper focuses on extending drug release duration from contact lenses by incorporating catanionic aggregates. The aggregates consist of a long-chain cationic surfactant, i.e., cetalkonium chloride (CKC), and an oppositely charged anti-inflammatory amphiphilic drug. We studied three non-steroidal anti-inflammatory (NSAID) drugs with different octanol-water partition coefficients; diclofenac sodium (DFNa), flurbiprofen sodium (FBNa), and naproxen sodium (NPNa). Confirmation of catanionic aggregate formation in solution was determined by steady and dynamic shear rheology measurements. We observed the increased viscosity, shear thinning, and viscoelastic behavior characteristic of wormlike micelles; the rheological data are reasonably well described using a Maxwellian fluid model with a single relaxation time. In vitro release experiments demonstrated that the extension in the drug release time is dependent on the ability of a drug to form viscoelastic catanionic aggregates. Such aggregates retard the diffusive transport of drug molecules from the contact lenses. Our study revealed that the release kinetics depends on the CKC concentration and the alkyl chain length of the cationic surfactant. We demonstrated that more hydrophobic drugs such as diclofenac sodium show a more extended release than less hydrophobic drugs such as naproxen sodium.
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http://dx.doi.org/10.3390/biom9100593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843253PMC
October 2019

Decoupling Ionic and Electronic Pathways in Low-Dimensional Hybrid Conductors.

J Am Chem Soc 2019 Nov 24;141(44):17830-17837. Epub 2019 Oct 24.

Department of Materials Science and Engineering , University of Maryland , College Park , Maryland 20742 , United States.

The construction of two-dimensional (2D) layered compounds for nanofluidic ion transport has recently attracted increasing interest due to the facile fabrication, tunable channel size, and high flux of these materials. Here we design a nacre-mimetic graphite-based nanofluidic structure in which the nanometer-thick graphite flakes are wrapped by negatively charged nanofibrillated cellulose (NFC) fibers to form multiple 2D confined spacings as nanochannels for rapid cation transport. At the same time, the graphite-NFC structure exhibits an ultralow electrical conductivity (σ ≤ 10 S/cm), even when the graphite concentration is up to 50 wt %, well above the percolation threshold (∼1 wt %). By tuning the hydration degree of graphite-NFC composites, the surface-charge-governed ion transport in the confined ∼1 nm spacings exhibits nearly 12 times higher ionic conductivity (1 × 10 S/cm) than that of a fully swollen structure (∼1.5 nm, 8.5 × 10 S/cm) at salt concentrations up to 0.1 M. The resulting charge selective conductor shows intriguing features of both high ionic conductivity and low electrical conductivity. Moreover, the inherent stability of the graphite and NFC components contributes to the strong functionality of the nanofluidic ion conductors in both acidic and basic environments. Our work demonstrates this 1D-2D material hybrid system as a suitable platform to study nanofluidic ion transport and provides a promising strategy to decouple ionic and electronic pathways, which is attractive for applications in new nanofluidic device designs.
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http://dx.doi.org/10.1021/jacs.9b09009DOI Listing
November 2019

Molecular partitioning in ternary solutions of cellulose.

Carbohydr Polym 2019 Sep 23;220:157-162. Epub 2019 May 23.

Department of Materials Science and Engineering, University of Maryland, College Park, MD, 20742, United States; Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD, 20899, United States. Electronic address:

Neutron scattering measurements on the structure and dynamics of ternary solutions of microcrystalline cellulose (MC) in mixtures of an ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate and a polar organic solvent dimethylformamide (DMF) have shown that MC can be fully dissolved in solvent mixtures. Data also show the molecular partitioning of IL into coexisting states. The structure partitioning is manifested as IL adsorbed to cellulose molecules with additional IL self-assembled to form clusters in solution, while the dynamics partitioning shows dynamical heterogeneities of the IL with slow dynamics resembling neat IL and fast dynamics being coupled with the solvent. The composition dependence of the molecular partitioning results in a solubility gap in dilute cellulose solutions and a phase boundary criterion of the molar ratio of IL / MC ∼ 3 in more concentrated regimes. The two characteristics together define the main features of the dissolution phase diagram of ternary cellulose mixtures of MC / IL / DMF at the room temperature.
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http://dx.doi.org/10.1016/j.carbpol.2019.05.054DOI Listing
September 2019

Cellulose ionic conductors with high differential thermal voltage for low-grade heat harvesting.

Nat Mater 2019 06 25;18(6):608-613. Epub 2019 Mar 25.

Department of Materials Science and Engineering, University of Maryland College Park, College Park, MD, USA.

Converting low-grade heat into useful electricity requires a technology that is efficient and cost effective. Here, we demonstrate a cellulosic membrane that relies on sub-nanoscale confinement of ions in oxidized and aligned cellulose molecular chains to enhance selective diffusion under a thermal gradient. After infiltrating electrolyte into the cellulosic membrane and applying an axial temperature gradient, the ionic conductor exhibits a thermal gradient ratio (analogous to the Seebeck coefficient in thermoelectrics) of 24 mV K-more than twice the highest value reported until now. We attribute the enhanced thermally generated voltage to effective sodium ion insertion into the charged molecular chains of the cellulosic membrane, which consists of type II cellulose, while this process does not occur in natural wood or type I cellulose. With this material, we demonstrate a flexible and biocompatible heat-to-electricity conversion device via nanoscale engineering based on sustainable materials that can enable large-scale manufacture.
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http://dx.doi.org/10.1038/s41563-019-0315-6DOI Listing
June 2019

A nanofluidic ion regulation membrane with aligned cellulose nanofibers.

Sci Adv 2019 Feb 22;5(2):eaau4238. Epub 2019 Feb 22.

Department of Materials Science and Engineering, University of Maryland College Park, College Park, MD 20742, USA.

The advancement of nanofluidic applications will require the identification of materials with high-conductivity nanoscale channels that can be readily obtained at massive scale. Inspired by the transpiration in mesostructured trees, we report a nanofluidic membrane consisting of densely packed cellulose nanofibers directly derived from wood. Numerous nanochannels are produced among an expansive array of one-dimensional cellulose nanofibers. The abundant functional groups of cellulose enable facile tuning of the surface charge density via chemical modification. The nanofiber-nanofiber spacing can also be tuned from ~2 to ~20 nm by structural engineering. The surface-charge-governed ionic transport region shows a high ionic conductivity plateau of ~2 mS cm (up to 10 mM). The nanofluidic membrane also exhibits excellent mechanical flexibility, demonstrating stable performance even when the membrane is folded 150°. Combining the inherent advantages of cellulose, this novel class of membrane offers an environmentally responsible strategy for flexible and printable nanofluidic applications.
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http://dx.doi.org/10.1126/sciadv.aau4238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386557PMC
February 2019

Neutron scattering in the biological sciences: progress and prospects.

Acta Crystallogr D Struct Biol 2018 Dec 20;74(Pt 12):1129-1168. Epub 2018 Dec 20.

Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, USA.

The scattering of neutrons can be used to provide information on the structure and dynamics of biological systems on multiple length and time scales. Pursuant to a National Science Foundation-funded workshop in February 2018, recent developments in this field are reviewed here, as well as future prospects that can be expected given recent advances in sources, instrumentation and computational power and methods. Crystallography, solution scattering, dynamics, membranes, labeling and imaging are examined. For the extraction of maximum information, the incorporation of judicious specific deuterium labeling, the integration of several types of experiment, and interpretation using high-performance computer simulation models are often found to be particularly powerful.
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http://dx.doi.org/10.1107/S2059798318017503DOI Listing
December 2018

Phase Separation and Stack Alignment in Aqueous Cellulose Nanocrystal Suspension under Weak Magnetic Field.

Langmuir 2018 07 29;34(27):8042-8051. Epub 2018 Jun 29.

Department of Materials Science and Engineering , University of Maryland , College Park , Maryland 20742 , United States.

Isotropic-nematic (I-N) transitions in cellulose nanocrystal (CNC) suspension and self-assembled structures in the isotropic and nematic phases were investigated using scattering and microscopy methods. A CNC suspension with a mass fraction of 7.4% spontaneously phase separated into an isotropic phase of 6.9% in the top layer and a nematic phase of 7.9% in the bottom layer. In both the phases, the CNC particles formed stacks with an interparticle distance being of ≈37 nm. One-dimensional small-angle neutron scattering (SANS) profiles due to both phases could be fitted using a stacking model considering finite particle sizes. SANS and atomic force microscopy studies indicate that the nematic phase in the bottom layer contains more populations of larger particles. A weak magnetic field of ≈0.5 T was able to induce a preferred orientation of CNC stacks in the nematic phase, with the stack normals being aligned with the field (perpendicular to the long axis of CNC particles). The Hermans orientation parameter, ⟨ P⟩, was ≈0.5 for the nematic phase; it remained unchanged during the relaxation process of ≈10 h. The fraction of oriented CNC populations decreased during the relaxation; dramatic decrease occurred in the first 3 h. The top layer remained isotropic in the weak field. Polarized microscopy studies revealed that the nematic phase was chiral. Adjacent particles in a stack form a twisting angle of ≈0.6 °, resulting in a helix pitch distance of ≈22 μm.
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http://dx.doi.org/10.1021/acs.langmuir.8b01452DOI Listing
July 2018

Spray-Processed Composites with High Conductivity and Elasticity.

ACS Appl Mater Interfaces 2018 Apr 11;10(16):13953-13962. Epub 2018 Apr 11.

Electrochemistry Branch, Sensor and Electron Devices Directorate, Power and Energy Division , U.S. Army Research Laboratory , Adelphi , Maryland 20783 , United States.

Highly conductive elastic composites were constructed using multistep solution-based fabrication methods that included the deposition of a nonwoven polymer fiber mat through solution blow spinning and nanoparticle nucleation. High nanoparticle loading was achieved by introducing silver nanoparticles into the fiber spinning solution. The presence of the silver nanoparticles facilitates improved uptake of silver nanoparticle precursor in subsequent processing steps. The precursor is used to generate a second nanoparticle population, leading to high loading and conductivity. Establishing high nanoparticle loading in a microfibrous block copolymer network generated deformable composites that can sustain electrical conductivities reaching 9000 S/cm under 100% tensile strain. These conductive elastic fabrics can retain at least 70% of their initial electrical conductivity after being stretched to 100% strain and released for 500 cycles. This composite material system has the potential to be implemented in wearable electronics and robotic systems.
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http://dx.doi.org/10.1021/acsami.8b00068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241284PMC
April 2018

Entropic stabilization of folded RNA in crowded solutions measured by SAXS.

Nucleic Acids Res 2016 Nov 4;44(19):9452-9461. Epub 2016 Jul 4.

T. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA

Non-coding RNAs must fold into specific structures that are stabilized by metal ions and other co-solutes in the cell's interior. Large crowder molecules such as PEG stabilize a bacterial group I ribozyme so that the RNA folds in low Mg concentrations typical of the cell's interior. To understand the thermodynamic origins of stabilization by crowder molecules, small angle X-ray scattering was used to measure the folding and helix assembly of a bacterial group I ribozyme at different temperatures and in different MgCl and polyethylene glycol (PEG) concentrations. The resulting phase diagrams show that perturbations to folding by each variable do not overlap. A favorable enthalpy change drives the formation of compact, native-like structures, but requires Mg ions at all temperatures studied (5-55°C). PEG reduces the entropic cost of helix assembly and increases correlations between RNA segments at all temperatures. The phase diagrams also revealed a semi-compact intermediate between the unfolded and folded ensemble that is locally more flexible than the unfolded state, as judged by SHAPE modification. These results suggest that environmental variables such as temperature and solute density will favor different types of RNA structures.
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http://dx.doi.org/10.1093/nar/gkw597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100557PMC
November 2016

Molecular crowding overcomes the destabilizing effects of mutations in a bacterial ribozyme.

Nucleic Acids Res 2015 Jan 24;43(2):1170-6. Epub 2014 Dec 24.

Thomas C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD 21218, USA

The native structure of the Azoarcus group I ribozyme is stabilized by the cooperative formation of tertiary interactions between double helical domains. Thus, even single mutations that break this network of tertiary interactions reduce ribozyme activity in physiological Mg(2+) concentrations. Here, we report that molecular crowding comparable to that in the cell compensates for destabilizing mutations in the Azoarcus ribozyme. Small angle X-ray scattering, native polyacrylamide gel electrophoresis and activity assays were used to compare folding free energies in dilute and crowded solutions containing 18% PEG1000. Crowder molecules allowed the wild-type and mutant ribozymes to fold at similarly low Mg(2+) concentrations and stabilized the active structure of the mutant ribozymes under physiological conditions. This compensation helps explains why ribozyme mutations are often less deleterious in the cell than in the test tube. Nevertheless, crowding did not rescue the high fraction of folded but less active structures formed by double and triple mutants. We conclude that crowding broadens the fitness landscape by stabilizing compact RNA structures without improving the specificity of self-assembly.
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http://dx.doi.org/10.1093/nar/gku1335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333387PMC
January 2015

NMR Water Self-Diffusion and Relaxation Studies on Sodium Polyacrylate Solutions and Gels in Physiologic Ionic Solutions.

J Appl Polym Sci 2014 Mar;131(6)

Section on Tissue Biophysics and Biomimetics, Program in Pediatric Imaging and Tissue Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.

Water self-diffusion coefficients and longitudinal relaxation rates in sodium polyacrylate solutions and gels were measured by NMR, as a function of polymer content and structure in a physiological concentration range of monovalent and divalent cations, Ca and Na. Several physical models describing the self-diffusion of the solvent were applied and compared. A free-volume model was found to be in good agreement with the experimental results over a wide range of polymer concentrations. The longitudinal relaxation rate exhibited linear dependence on polymer concentration below a critical concentration and showed non-linear behavior at higher concentrations. Both the water self-diffusion and relaxation were less influenced by the polymer in the gel state than in the uncrosslinked polymer solutions. The effect of Na on the mobility of water molecules was practically undetectable. By contrast, addition of Ca strongly increased the longitudinal relaxation rate while its effect on the self-diffusion coefficient was much less pronounced.
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http://dx.doi.org/10.1002/app.40001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882160PMC
March 2014

Morphotropic phase boundaries in ferromagnets: Tb(1-x)Dy(x)Fe2 alloys.

Phys Rev Lett 2013 Jul 3;111(1):017203. Epub 2013 Jul 3.

Department of Materials Science and Engineering, University of Maryland, College Park, Maryland 20742, USA.

The structure and properties of the ferromagnet Tb(1-x)Dy(x)Fe(2) are explored through the morphotropic phase boundary (MPB) separating ferroic phases of differing symmetry. Our synchrotron data support a first order structural transition, with a broadening MPB width at higher temperatures. The optimal point for magnetomechanical applications is not centered on the MPB but lies on the rhombohedral side, where the high striction of the rhombohedral majority phase combines with the softened anisotropy of the MPB. We compare our findings with single ion crystal field theory and with ferroelectric MPBs, where the controlling energies are different.
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http://dx.doi.org/10.1103/PhysRevLett.111.017203DOI Listing
July 2013

Crowders perturb the entropy of RNA energy landscapes to favor folding.

J Am Chem Soc 2013 Jul 1;135(27):10055-63. Epub 2013 Jul 1.

T. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.

Biological macromolecules have evolved to fold and operate in the crowded environment of the cell. We have shown previously that molecular crowding stabilizes folded RNA structures. Here we report SAXS measurements on a 64 kDa bacterial group I ribozyme in the presence of mono- and divalent ions and PEG crowders of different molecular weight. These experiments show that crowders always stabilize the folded RNA, but this stabilization is weaker in NaCl solutions than MgCl2 solutions. Additionally, we find that RNAs with the same global structure, parametrized by Rg, have different scattering functions depending upon the ratio of electrostatic and entropic stabilization by ions and crowders, respectively. We quantify this difference using the scattering length per scattering volume and find that this ratio is larger for RNAs that fold in lower ionic strength solutions due to the higher crowder content. We conclude that lower RNA flexibility, or reduced configurational entropy, widens the free energy gap between the unfolded and folded RNA in crowded MgCl2 solutions.
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http://dx.doi.org/10.1021/ja4030098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773054PMC
July 2013

Self-assembled block copolymer photonic crystal for selective fructose detection.

Biosens Bioelectron 2013 Aug 7;46:124-9. Epub 2013 Mar 7.

Fischell Department of Bioengineering, Room 2330 Jeong H. Kim Engineering Building, University of Maryland, College Park, MD 20742, USA.

The use of one-dimensional photonic crystals fabricated from a self-assembled lamellar block copolymer as a sensitive and selective fructose sensor is investigated. The polystyrene-b-poly(2-vinyl pyridine) (PS-b-P2VP) films are functionalized with 2-(bromomethyl)phenylboronic acid. The boronic acid moiety confined within the lamellar morphology can reversibly bind to sugars such as fructose, imparting the photonic properties of the PS-b-P2VP film. The films exhibit a detection limit of 500 μM in water and 1mM in phosphate buffered saline. Exposure to a 50 mM solution of fructose invokes a highly visible color change from blue to orange. The films are also able to selectively recognize and respond to fructose in competitive studies in the presence of glucose, mannose and sucrose.
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http://dx.doi.org/10.1016/j.bios.2013.02.025DOI Listing
August 2013

Color changing block copolymer films for chemical sensing of simple sugars.

Biosens Bioelectron 2011 Oct 23;28(1):349-54. Epub 2011 Jul 23.

Fischell Department of Bioengineering Room 2330 Jeong H. Kim Engineering Building, University of Maryland, College Park, MD 20742, USA.

We investigated the use of functionalized photonic block copolymer films for the detection of glucose. Polystyrene-b-poly(2-vinyl pyridine) (PS-b-P2VP) block copolymers were chemically functionalized with 2-(bromomethyl)phenylboronic acid and cast into films that reflect a visible color when exposed to aqueous media. The 2-(bromomethyl)phenylboronic acid functionality can reversibly bind to glucose. When exposed to high concentrations of glucose the polymer responded with a red shift in color. Low concentration exposure of glucose caused the polymer films to blue shift in color. The BCP films also exhibited a selective response to fructose, mannose or galactose, giving a different response depending on which sugar is present. The color of the polymer was tuned to blue, green, yellow or orange by varying the film's crosslink density. The color change can be visually observed without the use of equipment such as a spectrometer.
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http://dx.doi.org/10.1016/j.bios.2011.07.043DOI Listing
October 2011

Multistage collapse of a bacterial ribozyme observed by time-resolved small-angle X-ray scattering.

J Am Chem Soc 2010 Jul;132(29):10148-54

Department of Materials Science and Engineering, University of Maryland, College Park, Maryland 20742, USA.

Ribozymes must fold into compact, native structures to function properly in the cell. The first step in forming the RNA tertiary structure is the neutralization of the phosphate charge by cations, followed by collapse of the unfolded molecules into more compact structures. The specificity of the collapse transition determines the structures of the folding intermediates and the folding time to the native state. However, the forces that enable specific collapse in RNA are not understood. Using time-resolved SAXS, we report that upon addition of 5 mM Mg(2+) to the Azoarcus group I ribozyme up to 80% of chains form compact structures in less than 1 ms. In 1 mM Mg(2+), the collapse transition produces extended structures that slowly approach the folded state, while > or = 1.5 mM Mg(2+) leads to an ensemble of random coils that fold with multistage kinetics. Increased flexibility of molecules in the intermediate ensemble correlates with a Mg(2+)-dependent increase in the fast folding population and a previously unobserved crossover in the collapse kinetics. Partial denaturation of the unfolded RNA with urea also increases the fraction of chains following the fast-folding pathway. These results demonstrate that the preferred collapse mechanism depends on the extent of Mg(2+)-dependent charge neutralization and that non-native interactions within the unfolded ensemble contribute to the heterogeneity of the ribozyme folding pathways at the very earliest stages of tertiary structure formation.
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http://dx.doi.org/10.1021/ja103867pDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918669PMC
July 2010

Molecular crowding stabilizes folded RNA structure by the excluded volume effect.

J Am Chem Soc 2010 Jun;132(25):8690-6

T. C. Jenkins Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218, USA.

Crowder molecules in solution alter the equilibrium between folded and unfolded states of biological macromolecules. It is therefore critical to account for the influence of these other molecules when describing the folding of RNA inside the cell. Small angle X-ray scattering experiments are reported on a 64 kDa bacterial group I ribozyme in the presence of polyethylene-glycol 1000 (PEG-1000), a molecular crowder with an average molecular weight of 1000 Da. In agreement with expected excluded volume effects, PEG favors more compact RNA structures. First, the transition from the unfolded to the folded (more compact) state occurs at lower MgCl(2) concentrations in PEG. Second, the radius of gyration of the unfolded RNA decreases from 76 to 64 A as the PEG concentration increases from 0 to 20% wt/vol. Changes to water and ion activities were measured experimentally, and theoretical models were used to evaluate the excluded volume. We conclude that the dominant influence of the PEG crowder on the folding process is the excluded volume effect.
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http://dx.doi.org/10.1021/ja101500gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906142PMC
June 2010

Dynamic transition in tRNA is solvent induced.

J Am Chem Soc 2006 Jan;128(1):32-3

Department of Biophysics, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218-2685, USA.

Dynamics of tRNA was studied using neutron scattering spectroscopy. Despite vast differences in the architecture and backbone structure of proteins and RNA, hydrated tRNA undergoes the dynamic transition at the same temperature as hydrated lysozyme. The similarity of the dynamic transition in RNA and proteins supports the idea that it is solvent induced. Because tRNA essentially has no methyl groups, the results also suggest that methyl groups are not the main contributor of the dynamic transition in biological macromolecules. However, they may explain strong differences in the dynamics of tRNA and lysozyme observed at low temperatures.
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http://dx.doi.org/10.1021/ja056444iDOI Listing
January 2006

RNA tertiary interactions mediate native collapse of a bacterial group I ribozyme.

J Mol Biol 2005 Nov 23;353(5):1199-209. Epub 2005 Sep 23.

Department of Chemistry, Johns Hopkins University, 3400 N. Charles St, Baltimore, MD 21218-2685, USA.

Large RNAs collapse into compact intermediates in the presence of counterions before folding to the native state. We previously found that collapse of a bacterial group I ribozyme correlates with the formation of helices within the ribozyme core, but occurs at Mg2+ concentrations too low to support stable tertiary structure and catalytic activity. Here, using small-angle X-ray scattering, we show that Mg2+-induced collapse is a cooperative folding transition that can be fit by a two-state model. The Mg2+ dependence of collapse is similar to the Mg2+ dependence of helix assembly measured by partial ribonuclease T1 digestion and of an unfolding transition measured by UV hypochromicity. The correspondence between multiple probes of RNA structure further supports a two-state model. A mutation that disrupts tertiary contacts between the L9 tetraloop and its helical receptor destabilized the compact state by 0.8 kcal/mol, while mutations in the central triplex were less destabilizing. These results show that native tertiary interactions stabilize the compact folding intermediates under conditions in which the RNA backbone remains accessible to solvent.
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http://dx.doi.org/10.1016/j.jmb.2005.09.015DOI Listing
November 2005