- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Microtubule and mitosis dynamics
- Nanocluster Synthesis and Applications
- Gold and Silver Nanoparticles Synthesis and Applications
- RNA Interference and Gene Delivery
- Lipid Membrane Structure and Behavior
- Nanopore and Nanochannel Transport Studies
- Photosynthetic Processes and Mechanisms
- Force Microscopy Techniques and Applications
- Molecular Junctions and Nanostructures
- Microfluidic and Capillary Electrophoresis Applications
- Micro and Nano Robotics
- DNA Repair Mechanisms
- Cellular Mechanics and Interactions
- Bacteriophages and microbial interactions
- 14-3-3 protein interactions
- Microfluidic and Bio-sensing Technologies
- Cellular transport and secretion
- Bacterial Genetics and Biotechnology
- Electrostatics and Colloid Interactions
- DNA and Biological Computing
- Supramolecular Self-Assembly in Materials
- Proteoglycans and glycosaminoglycans research
- Protein Structure and Dynamics
University of California, Santa Barbara
2011-2022
California NanoSystems Institute
2008-2020
Santa Barbara City College
2015-2018
California Institute of Technology
2004-2006
University of Southern California
1997-2001
Rockefeller University
1996-1998
Southern California University for Professional Studies
1997
Princeton University
1994-1995
Isaac Newton Institute for Mathematical Sciences
1995
Massachusetts Institute of Technology
1992
DNA self-assembly provides a programmable bottom-up approach for the synthesis of complex structures from nanoscale components. Although nanotubes are fundamental form encountered in tile-based self-assembly, factors governing tube structure remain poorly understood. Here we report and characterize new type nanotube made double-crossover molecules (DAE-E tiles). Unmodified tubes range 7 to 20 nm diameter (4 10 tiles circumference), grow as long 50 μm with persistence length ∼4 μm, can be...
Control of cell proliferation is a fundamental aspect tissue physiology central to morphogenesis, wound healing, and cancer. Although many the molecular genetic factors are now known, system level regulation growth still poorly understood. A simple form inhibition encountered in vitro normally differentiating epithelial cultures known as “contact inhibition.” The study presented here provides quantitative characterization contact dynamics on tissue-wide single levels. Using long-term...
DNA-bound silver nanoemitters reside in single-stranded regions of the host DNA. Their fluorescence is sensitive to both DNA base sequence and its secondary structure. Fluorescence from individual emitters hosted by "hairpins", which are suitable for incorporation into scaffolds, detectable using standard epifluorescence techniques. Supporting information this article available on WWW under http://www.wiley-vch.de/contents/jc_2089/2008/c2380_s.pdf or author. Please note: The publisher not...
We have investigated the formation of phospholipid bilayers neutral (zwitterionic) lipid dimyristoyl-phosphatidylcholine (DMPC) on various glass surfaces from vesicles in aqueous solutions and temperatures using a number complementary techniques: surface forces apparatus (SFA), quartz crystal microbalance (QCM), fluorescence recovery after photobleaching (FRAP), microscopy, streaming potential (SP) measurements. The process involves five stages: vesicle adhesion to substrate via...
We observe quasistatic deformation of lipid vesicles from within, due to the polymerization confined microtubules. A pair long, narrow membrane sleeves appears, sheathing microtubule ends as they grow. Spontaneous buckling reveals that force generated can be greater than 2 pN. The evolution shape and magnitude are consistent with a simple theory for free energy. consider model generating mechanism in which thermal fluctuations ``rectified'' by binding tubulin dimers end.
Few-atom Ag clusters self-assemble on single-stranded DNA and exhibit sequence-dependent fluorescence ranging from the blue to NIR. sequence presents a very large parameter space for creating new Agn:DNA emitters, with potential improved chemical stability. Exploration of this may be greatly facilitated by identification classes emitters that share similar features, helping provide insight into their fluorescence-determining physical features. We synthesize hairpins 3 12 cytosines (C's) in...
We map the phase diagram of microtubules as a function temperature and tubulin concentration. observe spontaneous site-nucleated microtubule assembly. At temperatures concentrations below onset nucleation, we measure steady-state proportion occupied nucleation sites distribution lengths microtubules. Our observations reveal transition in length dynamics from bounded to unbounded growth. This is also evident individual The assembly completes diagram. concentration dependence latent time for bulk.
We study microtubules in vesicles using micropipet aspiration. A single microtubule a vesicle buckles as aspiration increases the tension membrane, yielding measure of persistence length, 6.3 mm. linear bundle deforms membrane into shape Greek letter $\ensuremath{\varphi}$. Under tension, this undergoes an abrupt and irreversible transition to sphere are reorganized peripheral ring.
DNA nanotubes are crystalline self-assemblies of tiles ∼10 nm in diameter that readily grow tens micrometers length. Easy assembly, programmability, and stiffness make them interesting for many applications, but begin to melt at temperatures below 40 °C, break open when deposited on mica or scanned by AFM, disintegrate deionized water. These weaknesses can be traced the presence discontinuities phosphate backbone, called nicks. The studied here have five nicks, one core a tile each corner....
We measure the stiffness of tiled DNA nanotubes (HX-tubes) as a function their (defined) circumference by analyzing micrometer-scale thermal deformations using fluorescence microscopy. derive model that relates nanoscale features HX-tube architecture to measured persistence lengths. Given known double-stranded DNA, we use this constrain average spacing between and effective individual duplexes in tube. A key structural feature can affect is potential form with discrete amounts twist about...
We report UV excitation through the DNA bases as a universal pathway to visible emission from stabilized silver cluster fluorophores (AgDNAs). AgDNAs with peak emissions throughout spectrum all exhibit two peaks in fluorescence excitation: at wavelength 50–150 nm shorter than and between 260 270 depending on specifics of strand. produces same 2–4 times greater intensity specific emitter. The excellent agreement AgDNA absorption spectra, similarity bare ubiquity for studied strongly suggest...
Influenza is a severe disease in humans and animals with few effective therapies available. All strains of influenza virus are prone to developing drug resistance due the high mutation rate viral genome. A therapeutic agent that targets highly conserved region could bypass also be against multiple influenza. uses many individually weak ligand binding interactions for avidity multivalent attachment sialic acid-bearing cells. Polymerized acid analogs can form but not ideal therapeutics...
Liquid-liquid phase separation of a polymer-rich from polymer-dilute solution, known generally as coacervation, has been observed in variety biomolecular systems. Understanding this process, and the properties resulting liquid, hampered typical systems by complexity components intermolecular interactions. Here, we examine single-component system comprised entirely DNA, which tetravalent DNA nanostar particles condense into liquids through attractive bonds formed basepairing We measure...
We have measured the effect of tension on dimerization kinetics channel-forming peptide gramicidin A. By aspirating large unilamellar vesicles into a micropipette electrode, we are able to simultaneously monitor membrane and electrical activity. find that dimer formation rate increases by factor 5 as ranges from 0 4 dyn/cm. The lifetime also with tension. This behavior is well described phenomenological model elasticity in which modulates mismatch thickness between membrane.
The fidelity of Escherichia coli DNA polymerase III (pol III) is measured and the effects β, γ processivity ε proofreading subunits are evaluated using a gel kinetic assay. Pol holoenzyme synthesizes with extremely high fidelity, misincorporating dTMP, dAMP, dGMP opposite template G target efficiencies f inc = 5.6 × 10−6, 4.2 10−7, 7 respectively. Elevated dGMP·G dTMP·G misincorporation 3.2 10−5 5.8 10−4, attributed to "dNTP-stabilized" misalignment mechanism, occur when C A, respectively,...
Among the key goals of structural DNA nanotechnology are to build highly ordered structures self-assembled from individual motifs in 1D, 2D, and finally 3D. All three these have been achieved with a variety motifs. Here, we report design characterization 1D nanotubes 2D arrays assembled novel motifs, 6-helix bundle (6HB), flanked by two helices same plane (6HB+2), trigonal arrangement (6HB+3). Long all Such likely applications nanotechnology, so it is important characterize their physical...
Silver–DNA nanoclusters (Ag:DNAs) are novel fluorophores under active research and development as alternative biomolecular markers. Comprised of a few-atom Ag cluster that is stabilized in water by binding to strand DNA, they also interesting for fundamental explorations into the properties metal molecules. Here, we use situ calibrated electrokinetic microfluidics fluorescence correlation spectroscopy determine size, charge, conformation select set Ag:DNAs. Among them pair spectrally...
We show that DNA hairpins template the site-specific assembly of fluorescent few-atom Ag clusters on nanotubes. Fluorescent form only at hairpin sites and not double-stranded scaffold, allowing for spatially programmed self-assembly. synthesized protruding from nanotubes can have nearly identical fluorescence spectra to those free sequence. Analysis stepwise photobleaching individual suggests a chemical yield ~45%. Given well-established sequence-specific optical properties stabilized...
The classic picture of soft material mechanics is that rubber elasticity, in which modulus related to the entropic elasticity flexible polymeric linkers. model, however, largely ignores role valence (i.e., number network chains emanating from a junction). Recent work predicts valence, and particularly Maxwell isostatic point, plays key determining semiflexible polymer networks. Here, we report series experiments confirming prominent model system. system based on DNA nanostars (DNAns):...
We present the first direct observations of tile-based DNA self-assembly in solution using fluorescent nanotubes composed a single tile. The reach tens microns length by end-to-end joining rather than sequential addition tiles. Their exponential distributions withstand dilution but decay via scission upon heating, with an energy barrier ${E}_{\mathrm{s}\mathrm{c}}\ensuremath{\sim}180{k}_{B}T$. are thus uniquely accessible equilibrium polymers that enable new approaches to optimizing...
Cells are capable of a variety dramatic stimuli-responsive mechanical behaviors. These capabilities enabled by the pervading cytoskeletal network, an active gel composed structural filaments (e.g., actin) that acted upon motor proteins myosin). Here, we describe synthesis and characterization using noncytoskeletal components. We use methods base-pair-templated DNA self assembly to create hybrid containing stiff tubes flexible linkers. then activate adding FtsK50C, construct derived from...
Neurotransmitters are small molecules that orchestrate complex patterns of brain activity. Unfortunately, there exist few sensors capable directly detecting individual neurotransmitters. Those do either unspecific or fail to capture the temporal spatial dynamics neurotransmitter release. DNA-stabilized silver nanoclusters (DNA-AgNCs) a new class biocompatible, fluorescent nanostructures have recently been shown offer promise as biosensors. In this work, we identify two different DNA...