Publications

2004
Gordon, V. D. ; Xi, C. ; Hutchinson, J. W. ; Bausch, A. R. ; Marquez, M. ; Weitz, D. A. Self-assembled polymer membrane capsules inflated by osmotic pressure. Journal of the American Chemical Society 2004, 126, 14117-14122.Abstract
We fabricate and characterize capsules that are composite membranes, made of a polymer network stabilized by adsorption to colloids and inflated by osmotic pressure from internal free polyelectrolyte; here, poly-L-lysine forms the network and inflates the capsules. To assess these capsules' properties and structure, we deform capsules using microcantilevers and use finite element modeling to describe these deformations. Additional experimental tests confirm the model's validity. These capsules' resilient response to mechanical forces indicates that loading and shear should be good triggers for the release of contents via deformation. The osmotic pressure inflating these capsules has the potential to trigger release of contents via deflation in response to changes in the capsules' environment; we demonstrate addition of salt as a trigger for deflating capsules. Because these capsules have a variety of release triggers available and the technique used to fabricate them is very flexible and allows high encapsulation efficiency, these capsules have very high potential for application in many areas.
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Times Cited: 64
Gardel, M. L. ; Shin, J. H. ; MacKintosh, F. C. ; Mahadevan, L. ; Matsudaira, P. ; Weitz, D. A. Elastic behavior of cross-linked and bundled actin networks. Science 2004, 304, 1301-1305.Abstract
Networks of cross-linked and bundled actin. laments are ubiquitous in the cellular cytoskeleton, but their elasticity remains poorly understood. We show that these networks exhibit exceptional elastic behavior that reflects the mechanical properties of individual. laments. There are two distinct regimes of elasticity, one reflecting bending of single. laments and a second reflecting stretching of entropic fluctuations of filament length. The mechanical stiffness can vary by several decades with small changes in cross-link concentration, and can increase markedly upon application of external stress. We parameterize the full range of behavior in a state diagram and elucidate its origin with a robust model.
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Times Cited: 427
Gardel, M. L. ; Shin, J. H. ; MacKintosh, F. C. ; Mahadevan, L. ; Matsudaira, P. A. ; Weitz, D. A. Scaling of F-actin network rheology to probe single filament elasticity and dynamics. Physical Review Letters 2004, 93.Abstract
The linear and nonlinear viscoelastic response of networks of cross-linked and bundled cytoskeletal filaments demonstrates remarkable scaling with both frequency and applied prestress, which helps elucidate the origins of the viscoelasticity. The frequency dependence of the shear modulus reflects the underlying single-filament relaxation dynamics for 0.1-10 rad/sec. Moreover, the nonlinear strain stiffening of such networks exhibits a universal form as a function of prestress; this is quantitatively explained by the full force-extension relation of single semiflexible filaments.
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Times Cited: 80
Fernandez-Nieves, A. ; Link, D. R. ; Rudhardt, D. ; Weitz, D. A. Electro-optics of bipolar nematic liquid crystal droplets. Physical Review Letters 2004, 92.Abstract
We directly visualize the response and relaxation dynamics of bipolar nematic liquid crystal droplets to an applied electric field E. Despite strong planar anchoring, there is no critical field for switching. Instead, upon application of E, the surface region first reorients, followed by movement of the disclinations and the bipolar axis. After removing E, elastic forces restore the drop to its original state. The collective electro-optic properties of ordered hexagonal-close-packed monolayers of drops are probed by diffraction experiments confirming the proposed switching mechanism.
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Times Cited: 45
Cohen, I. ; Mason, T. G. ; Weitz, D. A. Shear-induced configurations of confined colloidal suspensions. Physical Review Letters 2004, 93.Abstract
We show that geometric confinement dramatically affects the shear-induced configurations of dense monodisperse colloidal suspensions; a new structure emerges, where layers of particles buckle to stack in a more efficient packing. The volume fraction in the shear zone is controlled by a balance between the viscous stresses and the osmotic pressure of a contacting reservoir of unsheared particles. We present a model that accounts for our observations and helps elucidate the complex interplay between particle packing and shear stress for confined suspensions.
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Times Cited: 68
Cheng, Z. D. ; de las Nieves, A. F. ; Marquez, M. ; Weitz, D. A. ; Mason, T. G. ; Chaikin, P. M. Manipulation of microdisks in laser tweezers. In Optical Trapping and Optical Micromanipulation; Dholakia, K. ; Spalding, G. C., Ed. 2004; Vol. 5514, pp. 99-108.Abstract
Short thin cylinders can be the basic part of mesoscopic actuators powered by laser tweezers. We demonstrate that micro size birefringent colloidal coins can be positioned translationally and orientationally in advance of the prediction of current theoretical modeling. Circularly polarized laser tweezers keep driving the rotation of the microdisk. Viscous flow between a hard wall and a microdisk excites the disk to an oscillation orbit. These disks can be fabricated via solidification of emulsion drops by tuning temperature or solvent concentration so that molecules in the drop assuming a smectic phase.
Times Cited: 0 Conference on Optical Trapping and Optical Micromanipulation Aug 02-06, 2004 Denver, CO Spie
Aray, Y. ; Manuel, M. ; Rodriguez, J. ; Vega, D. ; Simon-Manso, Y. ; Coll, S. ; Gonzalez, C. ; Weitz, D. A. Electrostatics for exploring the nature of the hydrogen bonding in polyethylene oxide hydration. Journal of Physical Chemistry B 2004, 108, 2418-2424.Abstract
{Binding between water and models of poly(ethylene oxide), (CH2-CH2-O)(n)
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Times Cited: 31
2003
Zebrowski, J. ; Prasad, V. ; Zhang, W. ; Walker, L. M. ; Weitz, D. A. Shake-gels: Shear-induced gelation of laponite-PEO mixtures. Colloids and Surfaces a-Physicochemical and Engineering Aspects 2003, 213, 189-197.Abstract
Suspensions of clay particles (laponite), mixed with poly(ethylene oxide) (PEO) undergo a dramatic shear thickening when subjected to vigorous shaking, which transforms them from a low viscosity fluid into a 'shake-gel', a solid with elasticity sufficient enough to support its own weight. The shake-gel is reversible, relaxing back to a fluid with a relaxation time that is strongly dependent on PEO concentration. Shake-gels are observed for PEO concentrations slightly below the threshold for complete saturation of the laponite particles by the polymer. Light scattering measurements confirm that the PEO is adsorbed on the surface of the laponite particles, and suggests that shear induces a bridging between the colloidal particles, resulting in a gel network which spans the system. Desorption of the polymer reduces the bridging and thus relaxes the network. (C) 2002 Elsevier Science B.V. All rights reserved.
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Times Cited: 57
Tsapis, N. ; Bennett, D. ; O'Driscoll, K. ; Shea, K. ; Lipp, M. M. ; Fu, K. ; Clarke, R. W. ; Deaver, D. ; Yamins, D. ; Wright, J. ; et al. Direct lung delivery of para-aminosalicylic acid by aerosol particles. Tuberculosis 2003, 83, 379-385.Abstract
Para-aminosalicylic acid (PAS), a tuberculostatic agent, was formulated into large porous particles for direct delivery into the lungs via inhalation. These particles possess optimized physical properties for deposition throughout the respiratory tract, a drug loading of 95% by weight and physical stability over 4 weeks at elevated temperatures. Upon insufflation in rats, PAS concentrations were measured in plasma, lung lining fluid and homogenized whole lung tissue. Systemic drug concentrations peaked at 15 min, with a maximum plasma concentration of 11+/-1 mug/ml. The concentration in the lung lining fluid was 148 +/- 62 mug/ml at 15 min. Tissue concentrations were 65 +/- 20 mug/ml at 15 min and 3.2 +/- 0.2 mug/ml at 3 h. PAS was cleared within 3 h from the lung lining fluid and plasma but was still present at therapeutic concentrations in the lung tissue. These results suggest that inhalation delivery of PAS can potentially allow for a reduction in total dose delivered while providing for higher local and similar peak systemic drug concentrations as compared to those obtained upon oral PAS dosing. Similar particles could potentially be used for the delivery of additional anti-tuberculosis agents such as rifampicin, aminoglucosides or fluoroquinolones. (C) 2003 Elsevier Ltd. All rights reserved.
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Times Cited: 29
Rudhardt, D. ; Fernandez-Nieves, A. ; Link, D. R. ; Weitz, D. A. Phase switching of ordered arrays of liquid crystal emulsions. Applied Physics Letters 2003, 82, 2610-2612.Abstract
We report a fabrication method for producing interference-based electro-optic phase gratings that switch between diffracting and transparent states. The phase grating consists of a hexagonal-close-packed array of monodisperse emulsion drops of nematic liquid crystal, embedded in a polymer matrix. Monodisperse droplet size allows for fast switching at low electric fields. (C) 2003 American Institute of Physics.
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Times Cited: 42
Popp, A. K. ; Valentine, M. T. ; Kaplan, P. D. ; Weitz, D. A. Microscopic origin of light scattering in tissue. Applied Optics 2003, 42, 2871-2880.Abstract
A newly designed instrument, the static light-scattering (SLS) microscope, which combines light microscopy with SLS, enables us to characterize local light-scattering patterns of thin tissue sections. Each measurement is performed with an illumination beam of 70-mum diameter. On these length scales, tissue is not homogeneous. Both structural ordering and small heterogeneities contribute to the scattering signal. Raw SLS data consist of a two-dimensional intensity distribution map I(theta, phi), showing the dependence of the scattered intensity I on the scattering angle theta and the azimuthal angle D. In contrast to the majority of experiments and to simulations that consider only the scattering angle, we additionally perform an analysis of the azimuthal dependence I(phi). We estimate different contributions to the azimuthal scattering variation and show that a significant fraction of the azimuthal amplitude is the result of tissue structure. As a demonstration of the importance of the structure-dependent part of the azimuthal signal, we show that this function of the scattered light alone can be used to classify tissue types with surprisingly high specificity and sensitivity. (C) 2003 Optical Society of America.
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Times Cited: 22 Biomedical Topical Meeting of the Optical-Society-of-America 2002 Miami beach, fl Optl Soc Amer
Prasad, V. ; Trappe, V. ; Dinsmore, A. D. ; Segre, P. N. ; Cipelletti, L. ; Weitz, D. A. Universal features of the fluid to solid transition for attractive colloidal particles. Faraday Discussions 2003, 123, 1-12.Abstract
Attractive colloidal particles can exhibit a fluid to solid phase transition if the magnitude of the attractive interaction is sufficiently large, if the volume fraction is sufficiently high, and if the applied stress is sufficiently small. The nature of this fluid to solid transition is similar for many different colloid systems, and for many different forms of interaction. The jamming phase transition captures the common features of these fluid to solid translations, by unifying the behavior as a function of the particle volume fraction, the energy of interparticle attractions, and the applied stress. This paper describes the applicability of the jamming state diagram, and highlights those regions where the fluid to solid transition is still poorly understood. It also presents new data for gelation of colloidal particles with an attractive depletion interaction, providing more insight into the origin of the fluid to solid transition.
Times Cited: 99 General Meeting on Non-Equilibrium Behaviour of Colloidal Dispersions Sep 09-11, 2002 Edinburgh, scotland
Pautot, S. ; Frisken, B. J. ; Weitz, D. A. Production of unilamellar vesicles using an inverted emulsion. Langmuir 2003, 19, 2870-2879.Abstract
We investigate a method for the controlled assembly of unilamellar vesicles consisting of bilayers assembled one leaflet at a time. We use water-in-oil emulsions stabilized by the material for the inner leaflet and produce vesicles by passing the water droplets through a second oil-water interface, where they become coated with the outer leaflet. We have used this technique to form vesicles from lipids, mixed lipid and surfactant systems, and diblock copolymers. The stability of lipid-stabilized emulsions limits the range of sizes that can be produced and the vesicle yield; nevertheless, there are several advantages with this emulsion-based technique: It is possible to make unilamellar vesicles with sizes ranging from 100 nm to 1 mum. Moreover, the process allows for efficient encapsulation and ensures that the contents of the vesicles remain isolated from the continuous aqueous phase. To illustrate possible applications of this technique, we demonstrate the use of vesicles as microreactors where we polymerize actin through the addition of magnesium and show that the polymerization kinetics are unaffected by the encapsulation.
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Times Cited: 95
Pautot, S. ; Frisken, B. J. ; Weitz, D. A. Engineering asymmetric vesicles. Proceedings of the National Academy of Sciences of the United States of America 2003, 100, 10718-10721.Abstract
Vesicles are bilayers of lipid molecules enclosing a fixed volume of aqueous solution. Ubiquitous in cells, they can be produced in vitro to study the physical properties of biological membranes and for use in drug delivery and cosmetics. Biological membranes are, in fact, a fluid mosaic of lipids and other molecules; the richness of their chemical and mechanical properties in vivo is often dictated by an asymmetric distribution of these molecules. Techniques for vesicle preparation have been based on the spontaneous assembly of lipid bilayers, precluding the formation of such asymmetric structures. Partial asymmetry has been achieved only with chemical methods greatly restricting the study of the physical and chemical properties of asymmetric vesicles and their use in potential applications for drug delivery. Here we describe the systematic engineering of unilamellar vesicles assembled with two independently prepared monolayers; this process produces asymmetries as high as 95%. We demonstrate the versatility of our method by investigating the stability of the asymmetry. We also use it to engineer hybrid structures comprised of an inner leaflet of diblock copolymer and an independent lipid outer leaflet.
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Times Cited: 110
Pautot, S. ; Frisken, B. J. ; Cheng, J. X. ; Xie, X. S. ; Weitz, D. A. Spontaneous formation of lipid structures at oil/water lipid interfaces. Langmuir 2003, 19, 10281-10287.Abstract
We report the spontaneous formation of emulsion droplets and multilamellar concentric onions when a water drop is immersed into dodecane containing phospholipids. We show that the origin of the spontaneous emulsification is the formation of a semierystalline multilamellar film at the dodecane-water interface, which swells with water, shedding the emulsion and onion droplets. We use coherent anti-Stokes Raman scattering microscopy to determine that the shell of the onion structures is composed of partially hydrated concentric bilayers, and the core is composed of lipids, water, and dodecane.
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Times Cited: 35
Nikolaides, M. G. ; Bausch, A. R. ; Hsu, M. F. ; Dinsmore, A. D. ; Brenner, M. P. ; Gay, C. ; Weitz, D. A. Like-charged particles at liquid interfaces - Reply. Nature 2003, 424, 1014-1014.
Times Cited: 12
Kilfoil, M. L. ; Pashkovski, E. E. ; Masters, J. A. ; Weitz, D. A. Dynamics of weakly aggregated colloidal particles. Philosophical Transactions of the Royal Society of London Series a-Mathematical Physical and Engineering Sciences 2003, 361, 753-764.Abstract
We discuss the behaviour of the dynamics of colloidal particles with a weak attractive interparticle interaction that is induced through the addition of polymer to the solvent. We briefly review the description of their behaviour in terms of the jamming phase diagram, which parametrized the fluid-to-solid transition due to changes in volume fraction, attractive energy or applied stress. We focus on a discussion of ageing of the solid gels formed by these colloid-polymer mixtures. They exhibit a delayed collapse induced by gravity. The time evolution of the height of the sediment exhibits an unexpected scaling behaviour, suggesting a universal nature to this delayed collapse. We complement these measurements of the scaling of the collapse with microscopic investigations of the evolution of the structure of the network using confocal microscopy. These results provide new insight into the origin of this ageing behaviour.
Times Cited: 27 Meeting on Slow Dynamics in Soft Matter Sep 25-26, 2002 Royal soc, london, england
Hyatt, C. J. ; Mironov, S. F. ; Wellner, M. ; Berenfeld, O. ; Popp, A. K. ; Weitz, D. A. ; Jalife, J. ; Pertsov, A. M. Synthesis of voltage-sensitive fluorescence signals from three-dimensional myocardial activation patterns. Biophysical Journal 2003, 85, 2673-2683.Abstract
Voltage-sensitive fluorescent dyes are commonly used to measure cardiac electrical activity. Recent studies indicate, however, that optical action potentials (OAPs) recorded from the myocardial surface originate from a widely distributed volume beneath the surface and may contain useful information regarding intramural activation. The first step toward obtaining this information is to predict OAPs from known patterns of three-dimensional (3-D) electrical activity. To achieve this goal, we developed a two-stage model in which the output of a 3-D ionic model of electrical excitation serves as the input to an optical model of light scattering and absorption inside heart tissue. The two-stage model permits unique optical signatures to be obtained for given 3-D patterns of electrical activity for direct comparison with experimental data, thus yielding information about intramural electrical activity. To illustrate applications of the model, we simulated surface fluorescence signals produced by 3-D electrical activity during epicardial and endocardial pacing. We discovered that OAP upstroke morphology was highly sensitive to the transmural component of wave front velocity and could be used to predict wave front orientation with respect to the surface. These findings demonstrate the potential of the model for obtaining useful 3-D information about intramural propagation.
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Times Cited: 53
Gordon, V. D. ; Valentine, M. T. ; Gardel, M. L. ; Andor-Ardo, D. ; Dennison, S. ; Bogdanov, A. A. ; Weitz, D. A. ; Deisboeck, T. S. Measuring the mechanical stress induced by an expanding multicellular tumor system: A case study. Experimental Cell Research 2003, 289, 58-66.Abstract
Rapid volumetric growth and extensive invasion into brain parenchyma are hallmarks of malignant neuroepithelial tumors in vivo. Little is known, however, about the mechanical impact of the growing brain tumor on its microenvironment. To better understand the environmental mechanical response, we used multiparticle tracking methods to probe the environment of a dynamically expanding, multicellular brain tumor spheroid that grew for 6 days in a three-dimensional Matrigel-based in vitro assay containing 1.0-mum latex beads. These beads act as reference markers for the gel, allowing us to image the spatial displacement of the tumor environment using high-resolution time-lapse video microscopy. The results show that the volumetrically expanding tumor spheroid pushes the gel outward and that this tumor-generated pressure propagates to a distance greater than the initial radius of the tumor spheroid. Intriguingly, beads near the tips of invasive cells are displaced inward, toward the advancing invasive cells. Furthermore, this localized cell traction correlates with a marked increase in total invasion area over the observation period. This case study presents evidence that an expanding microscopic tumor system exerts both significant mechanical pressure and significant traction on its microenvironment. (C) 2003 Elsevier Science (USA). All rights reserved.
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Times Cited: 43
Gardel, M. L. ; Valentine, M. T. ; Crocker, J. C. ; Bausch, A. R. ; Weitz, D. A. Microrheology of entangled F-actin solutions. Physical Review Letters 2003, 91.Abstract
We measure the viscoelasticity of entangled F-actin over length scales between 1 and 100 mum using one- and two-particle microrheology, and directly identify two distinct microscopic contributions to the elasticity. Filament entanglements lead to a frequency-independent elastic modulus over an extended frequency range of 0.01-30 rad/sec; this is probed with one-particle microrheology. Longitudinal fluctuations of the filaments increase the elastic modulus between 0.1 and 30 rad/sec at length scales up to the filament persistence length; this is probed by two-particle microrheology.
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Times Cited: 137

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