Publications by Year: 2014

2014
Chen, L. ; Li, Y. ; Fan, J. ; Bisoyi, H. K. ; Weitz, D. A. ; Li, Q. Photoresponsive Monodisperse Cholesteric Liquid Crystalline Microshells for Tunable Omnidirectional Lasing Enabled by a Visible Light-Driven Chiral Molecular Switch. Advanced Optical Materials 2014, 2 845-848. Publisher's VersionAbstract

A self‐organized, phototunable 3D photonic superstructure is fabricated from a photoresponsive 1D liquid crystal using microfluidics. The resulting microshells are water–oil–water double emulsions, in which the oil phase consists of the photoresponsive liquid crystals. The cholesteric microshells exhibit band‐edge lasing in all directions, and the wavelength of the resultant band‐edge laser is tuned via the pumping laser, causing photoisomerization of the chiral molecular switch.

chen2014.pdf
Arriaga, L. R. ; Datta, S. S. ; Kim, S. - H. ; Amstad, E. ; Kodger, T. E. ; Monroy, F. ; Weitz, D. A. Ultrathin Shell Double Emulsion Templated Giant Unilamellar Lipid Vesicles with Controlled Microdomain Formation. Small 2014, 10, 950–956. Publisher's VersionAbstract

A microfluidic approach is reported for the high-throughput, continuous production of giant unilamellar vesicles (GUVs) using water-in-oil-in-water double emulsion drops as templates. Importantly, these emulsion drops have ultrathin shells; this minimizes the amount of residual solvent that remains trapped within the GUV membrane, overcoming a major limitation of typical microfluidic approaches for GUV fabrication. This approach enables the formation of microdomains, characterized by different lipid compositions and structures within the GUV membranes. This work therefore demonstrates a straightforward and versatile approach to GUV fabrication with precise control over the GUV size, lipid composition and the formation of microdomains within the GUV membrane.

arriaga2014.pdf
Cohen, S. I. A. ; Rajah, L. ; Yoon, C. H. ; Buell, A. K. ; White, D. A. ; Sperling, R. A. ; Vendruscolo, M. ; Terentjev, E. M. ; Dobson, C. M. ; Weitz, D. A. ; et al. Spatial Propagation of Protein Polymerization. Physical Review Letters 2014, 112, 098101. Publisher's VersionAbstract

We consider the spatial dependence of filamentous protein self-assembly. Through studying the cases where the spreading of aggregated material is dominated either by diffusion or by growth, we derive analytical results for the spatial evolution of filamentous protein aggregation, which we validate against Monte Carlo simulations. Moreover, we compare the predictions of our theory with experimental measurements of two systems for which we identify the propagation as either growth or diffusion controlled. Our results connect the macroscopic observables that characterize the spatial propagation of protein self-assembly with the underlying microscopic processes and provide physical limits on spatial propagation and prionlike behavior associated with protein aggregation.

cohen2014.pdf
Jensen, M.  H. ; Morris, E.  J. ; Gallant, C.  M. ; Morgan, K.  G. ; Weitz, D.  A. ; Moore, J.  R. Mechanism of Calponin Stabilization of Cross-Linked Actin Networks. Biophysical Journal 2014, 106, 793 - 800. Publisher's VersionAbstract

The actin-binding protein calponin has been previously implicated in actin cytoskeletal regulation and is thought to act as an actin stabilizer, but the mechanism of its function is poorly understood. To investigate this underlying physical mechanism, we studied an in vitro model system of cross-linked actin using bulk rheology. Networks with basic calponin exhibited a delayed onset of strain stiffening (10.0% without calponin, 14.9% with calponin) and were able to withstand a higher maximal strain before failing (35% without calponin, 56% with calponin). Using fluorescence microscopy to study the mechanics of single actin filaments, we found that calponin increased the flexibility of actin filaments, evident as a decrease in persistence length from 17.6 μm without to 7.7 μm with calponin. Our data are consistent with current models of affine strain behavior in semiflexible polymer networks, and suggest that calponin stabilization of actin networks can be explained purely by changes in single-filament mechanics. We propose a model in which calponin stabilizes actin networks against shear through a reduction of persistence length of individual filaments.

jensen2014.pdf
Datta, S. S. ; Ramakrishnan, T. S. ; Weitz, D. A. Mobilization of a trapped non-wetting fluid from a three-dimensional porous medium. Physics of Fluids 2014, 26, 022002. Publisher's VersionAbstract

We use confocal microscopy to directly visualize the formation and complex morphologies of trapped non-wetting fluid ganglia within a model 3D porous medium. The wetting fluid continues to flow around the ganglia after they form; this flow is characterized by a capillary number, Ca. We find that the ganglia configurations do not vary for small Ca; by contrast, as Ca is increased above a threshold value, the largest ganglia start to become mobilized and are ultimately removed from the medium. By combining our 3D visualization with measurements of the bulk transport, we show that this behavior can be quantitatively understood by balancing the viscous forces exerted on the ganglia with the pore-scale capillary forces that keep them trapped within the medium. Our work thus helps elucidate the fluid dynamics underlying the mobilization of a trapped non-wetting fluid from a 3D porous medium.

datta2014.pdf
Comunian, T. A. ; Abbaspourrad, A. ; Favaro-Trindade, C. S. ; Weitz, D. A. Fabrication of solid lipid microcapsules containing ascorbic acid using a microfluidic technique. Food Chemistry 2014, 152, 271 - 275. Publisher's VersionAbstract

The importance of ascorbic acid (AA) in the human diet has motivated food researchers to develop AA-fortified food products. However, this compound is very unstable. The aim of this work was to produce solid lipid microcapsules (SLMs) loaded with AA using microfluidic technology. The morphology of the SLMs was analysed by optical, scanning electron and confocal microscopy. We determined the encapsulation efficiency, particle size and stability of the encapsulated material. Two different means of enhancing the encapsulation efficiency and stability of AA were demonstrated: a pore blocking method and a micromolecule-chelating agent within the core. The results indicated the enormous potential of the designed vehicle to prevent AA degradation in a food product; additionally, this vehicle could mask the acidic taste of AA.

comunian2014.pdf
Datta, S. S. ; Abbaspourrad, A. ; Amstad, E. ; Fan, J. ; Kim, S. - H. ; Romanowsky, M. ; Shum, H. C. ; Sun, B. J. ; Utada, A. S. ; Windbergs, M. ; et al. Double Emulsion Templated Solid Microcapsules: Mechanics And Controlled Release. Advanced Materials 2014, 26, 2205-2218. Publisher's VersionAbstract
We describe how droplet microfluidics can be used to fabricate solid-shelled microcapsules having precisely controlled release behavior. Glass capillary devices enable the production of monodisperse double emulsion drops, which can then be used as templates for microcapsule formation. The exquisite control afforded by microfluidics can be used to tune the compositions and geometrical characteristics of the microcapsules with exceptional precision. We review the use of this approach to fabricate microcapsules that only release their contents when exposed to a specific stimulus – such as a change in temperature, exposure to light, a change in the chemical environment, or an external stress – only after a prescribed time delay, and at a prescribed rate.
datta2014.pdf
Röding, M. ; Guo, M. ; Weitz, D. A. ; Rudemo, M. ; Särkkä, A. Identifying directional persistence in intracellular particle motion using Hidden Markov Models. Mathematical Biosciences 2014, 248, 140 - 145. Publisher's VersionAbstract

Particle tracking is a widely used and promising technique for elucidating complex dynamics of the living cell. The cytoplasm is an active material, in which the kinetics of intracellular structures are highly heterogeneous. Tracer particles typically undergo a combination of random motion and various types of directed motion caused by the activity of molecular motors and other non-equilibrium processes. Random switching between more and less directional persistence of motion generally occurs.

We present a method for identifying states of motion with different directional persistence in individual particle trajectories. Our analysis is based on a multi-scale turning angle model to characterize motion locally, together with a Hidden Markov Model with two states representing different directional persistence. We define one of the states by the motion of particles in a reference data set where some active processes have been inhibited.

We illustrate the usefulness of the method by studying transport of vesicles along microtubules and transport of nanospheres activated by myosin. We study the results using mean square displacements, durations, and particle speeds within each state. We conclude that the method provides accurate identification of states of motion with different directional persistence, with very good agreement in terms of mean-squared displacement between the reference data set and one of the states in the two-state model.

roding2014.pdf
Herranz-Blanco, B. ; Arriaga, L. R. ; Makila, E. ; Correia, A. ; Shrestha, N. ; Mirza, S. ; Weitz, D. A. ; Salonen, J. ; Hirvonen, J. ; Santos, H. A. Microfluidic assembly of multistage porous silicon-lipid vesicles for controlled drug release. Lab on a Chip 2014, 14, 1083 - 1086. Publisher's VersionAbstract

A reliable microfluidic platform for the generation of stable and monodisperse multistage drug delivery systems is reported. A glass-capillary flow-focusing droplet generation device was used to encapsulate thermally hydrocarbonized porous silicon (PSi) microparticles into the aqueous cores of double emulsion drops, yielding the formation of a multistage PSi-lipid vesicle. This composite system enables a large loading capacity for hydrophobic drugs.

herranz-blanco2014.pdf
Zhang, W. ; Seminara, A. ; Suaris, M. ; Brenner, M. P. ; Weitz, D. A. ; Angelini, T. E. Nutrient depletion in Bacillus subtilis biofilms triggers matrix production. New Journal of Physics 2014, 16, 015028. Publisher's VersionAbstract

Many types of bacteria form colonies that grow into physically robust and strongly adhesiveaggregates known as biofilms. A distinguishing characteristic of bacterial biofilms is an extracellular polymeric substance (EPS) matrix that encases the cells and provides physical integrity to the colony. The EPS matrix consists of a large amount of polysaccharide, as well as protein filaments, DNA and degraded cellular materials. The genetic pathways that control the transformation of a colony into a biofilm have been widely studied, and yield a spatiotemporal heterogeneity in EPS production. Spatial gradients in metabolites parallel this heterogeneity in EPS, but nutrient concentration as an underlying physiological initiator of EPS production has not been explored. Here, we study the role of nutrient depletion in EPS production in Bacillus subtilis biofilms. By monitoring simultaneously biofilm size and matrix production, we find that EPS production increases at a critical colony thickness that depends on the initial amount of carbon sources in the medium. Through studies of individual cells in liquid culture we find that EPS production can be triggered at the single-cell level by reducing nutrient concentration. To connect the single-cell assays with conditions in the biofilm, we calculate carbon concentration with a model for the reaction and diffusion of nutrients in the biofilm. This model predicts the relationship between the initial concentration of carbon and the thickness of the colony at the point of internal nutrient deprivation.

zhang2014.pdf
Campas, O. ; Mammoto, T. ; Hasso, S. ; Sperling, R. A. ; O'Connell, D. ; Bischof, A. G. ; Maas, R. ; Weitz, D. A. ; Mahadevan, L. ; Ingber, D. E. Quantifying cell-generated mechanical forces within living embryonic tissues. Nat Meth 2014, 11, 183 - 189. Publisher's VersionAbstract

Cell-generated mechanical forces play a critical role during tissue morphogenesis and organ formation in the embryo. Little is known about how these forces shape embryonic organs, mainly because it has not been possible to measure cellular forces within developing three-dimensional (3D) tissues in vivo. We present a method to quantify cell-generated mechanical stresses exerted locally within living embryonic tissues, using fluorescent, cell-sized oil microdroplets with defined mechanical properties and coated with adhesion receptor ligands. After a droplet is introduced between cells in a tissue, local stresses are determined from droplet shape deformations, measured using fluorescence microscopy and computerized image analysis. Using this method, we quantified the anisotropic stresses generated by mammary epithelial cells cultured within 3D aggregates, and we confirmed that these stresses (3.4 nN [mu]m-2) are dependent on myosin II activity and are more than twofold larger than stresses generated by cells of embryonic tooth mesenchyme, either within cultured aggregates or in developing whole mouse mandibles.

campas2014.pdf
Amstad, E. ; Datta, S. S. ; Weitz, D. A. The microfluidic post-array device: High throughput production of single emulsion drops. Lab on a Chip 2014, 14, 705-709. Publisher's VersionAbstract

We present a microfluidic device that enables high throughput production of relatively monodisperse emulsion drops while controlling the average size. The device consists of a two-dimensional array of regularly-spaced posts. Large drops of a highly polydisperse crude emulsion are input into the device and are successively split by the posts, ultimately yielding a finer emulsion consisting of smaller, and much more monodisperse drops. The size distribution of the resultant emulsion depends only weakly on the viscosities of the input fluids and allows fluids of very high viscosities to be used. The average size and polydispersity of the drops depend strongly on the device geometry enabling both control and optimization. We use this device to produce drops of a highly viscous monomer solution and subsequently solidify them into polymeric microparticles. The production rate of these devices is similar to that achieved by membrane emulsification techniques, yet the control over the drop size is superior; thus these post-array microfluidic devices are potentially useful for industrial applications.

amstad2014.pdf
Lee, M. ; Collins, J. W. ; Aubrecht, D. M. ; Sperling, R. A. ; Solomon, L. ; Ha, J. - W. ; Yi, G. - R. ; Weitz, D. A. ; Manoharan, V. N. Synchronized reinjection and coalescence of droplets in microfluidics. Lab on a Chip 2014, 14, 509-513. Publisher's VersionAbstract

Coalescence of two kinds of pre-processed droplets is necessary to perform chemical and biological assays in droplet-based microfluidics. However, a robust technique to accomplish this does not exist. Here we present a microfluidic device to synchronize the reinjection of two different kinds of droplets and coalesce them, using hydrostatic pressure in conjunction with a conventional syringe pump. We use a device consisting of two opposing T-junctions for reinjecting two kinds of droplets and control the flows of the droplets by applying gravity-driven hydrostatic pressure. The hydrostatic-pressure operation facilitates balancing the droplet reinjection rates and allows us to synchronize the reinjection. Furthermore, we present a simple but robust module to coalesce two droplets that sequentially come into the module, regardless of their arrival times. These re-injection and coalescence techniques might be used in lab-on-chip applications requiring droplets with controlled numbers of solid materials, which can be made by coalescing two pre-processed droplets that are formed and sorted in devices.

lee2014.pdf

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