Publications

2014
Jensen, K. E. ; Weitz, D. A. ; Spaepen, F. Local shear transformations in deformed and quiescent hard-sphere colloidal glasses. Physical Review E 2014, 90, 042305 -. Publisher's Version [PDF]
Zaburdaev, V. ; Biais, N. ; Schmiedeberg, M. ; Eriksson, J. ; Jonsson, A. - B. ; Sheetz, M.  P. ; Weitz, D.  A. Uncovering the Mechanism of Trapping and Cell Orientation during Neisseria gonorrhoeae Twitching Motility. 2014, 107, 1523 - 1531. Publisher's VersionAbstract

AbstractNeisseria gonorrheae bacteria are the causative agent of the second most common sexually transmitted infection in the world. The bacteria move on a surface by means of twitching motility. Their movement is mediated by multiple long and flexible filaments, called type IV pili, that extend from the cell body, attach to the surface, and retract, thus generating a pulling force. Moving cells also use pili to aggregate and form microcolonies. However, the mechanism by which the pili surrounding the cell body work together to propel bacteria remains unclear. Understanding this process will help describe the motility of N. gonorrheae bacteria, and thus the dissemination of the disease which they cause. In this article we track individual twitching cells and observe that their trajectories consist of alternating moving and pausing intervals, while the cell body is preferably oriented with its wide side toward the direction of motion. Based on these data, we propose a model for the collective pili operation of N. gonorrheae bacteria that explains the experimentally observed behavior. Individual pili function independently but can lead to coordinated motion or pausing via the force balance. The geometry of the cell defines its orientation during motion. We show that by changing pili substrate interactions, the motility pattern can be altered in a predictable way. Although the model proposed is tangibly simple, it still has sufficient robustness to incorporate further advanced pili features and various cell geometries to describe other bacteria that employ pili to move on surfaces.

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Larsen, R. J. ; Kim, J. - W. ; Zukoski, C. F. ; Weitz, D. A. Fluctuations in flow produced by competition between apparent wall slip and dilatancy. Rheologica Acta 2014, 53, 333-347. Publisher's Version [PDF]
Jarosz, D.  F. ; Brown, J.  C. S. ; Walker, G.  A. ; Datta, M.  S. ; Ung, W.  L. ; Lancaster, A.  K. ; Rotem, A. ; Chang, A. ; Newby, G.  A. ; Weitz, D.  A. ; et al. Cross-Kingdom Chemical Communication Drives a Heritable, Mutually Beneficial Prion-Based Transformation of Metabolism. Cell 2014, 158, 1083 - 1093. Publisher's VersionAbstract

Summary In experimental science, organisms are usually studied in isolation, but in the wild, they compete and cooperate in complex communities. We report a system for cross-kingdom communication by which bacteria heritably transform yeast metabolism. An ancient biological circuit blocks yeast from using other carbon sources in the presence of glucose. [GAR+], a protein-based epigenetic element, allows yeast to circumvent this “glucose repression” and use multiple carbon sources in the presence of glucose. Some bacteria secrete a chemical factor that induces [GAR+]. [GAR+] is advantageous to bacteria because yeast cells make less ethanol and is advantageous to yeast because their growth and long-term viability is improved in complex carbon sources. This cross-kingdom communication is broadly conserved, providing a compelling argument for its adaptive value. By heritably transforming growth and survival strategies in response to the selective pressures of life in a biological community, [GAR+] presents a unique example of Lamarckian inheritance.

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Wang, B. L. ; Ghaderi, A. ; Zhou, H. ; Agresti, J. ; Weitz, D. A. ; Fink, G. R. ; Stephanopoulos, G. Microfluidic high-throughput culturing of single cells for selection based on extracellular metabolite production or consumption. Nat Biotech 2014, 32, 473 - 478. Publisher's VersionAbstract

Phenotyping single cells based on the products they secrete or consume is a key bottleneck in many biotechnology applications, such as combinatorial metabolic engineering for the overproduction of secreted metabolites. Here we present a flexible high-throughput approach that uses microfluidics to compartmentalize individual cells for growth and analysis in monodisperse nanoliter aqueous droplets surrounded by an immiscible fluorinated oil phase. We use this system to identify xylose-overconsuming Saccharomyces cerevisiae cells from a population containing one such cell per 104 cells and to screen a genomic library to identify multiple copies of the xylose isomerase gene as a genomic change contributing to high xylose consumption, a trait important for lignocellulosic feedstock utilization. We also enriched L-lactate-producing Escherichia coli clones 5,800[times] from a population containing one L-lactate producer per 104D-lactate producers. Our approach has broad applications for single-cell analyses, such as in strain selection for the overproduction of fuels, chemicals and pharmaceuticals.

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Pessi, J. ; Santos, H. A. ; Miroshnyk, I. ; JoukoYliruusi, ; Weitz, D. A. ; Mirza, S. Microfluidics-assisted engineering of polymeric microcapsules with high encapsulation efficiency for protein drug delivery. International Journal of Pharmaceutics 2014, 472, 82 - 87. Publisher's VersionAbstract

Abstract In this study, microfluidic technology was employed to develop protein formulations. The microcapsules were produced with a biphasic flow to create water–oil–water (W/O/W) double emulsion droplets with ultrathin shells. Optimized microcapsule formulations containing 1% (w/w) bovine serum albumin (BSA) in the inner phase were prepared with poly(vinyl alcohol), polycaprolactone and polyethylene glycol. All the particles were found to be intact and with a particle size of 23–47 μm. Furthermore, the particles were monodisperse, non-porous and stable up to 4 weeks. The encapsulation efficiency of \{BSA\} in the microcapsules was 84%. The microcapsules released 30% of their content within 168 h. This study demonstrates that microfluidics is a powerful technique for engineering formulations for therapeutic proteins.

2014_intjpharm_pessi.pdf
Guo, M. ; Ehrlicher, A.  J. ; Jensen, M.  H. ; Renz, M. ; Moore, J.  R. ; Goldman, R.  D. ; Lippincott-Schwartz, J. ; Mackintosh, F.  C. ; Weitz, D.  A. Probing the Stochastic, Motor-Driven Properties of the Cytoplasm Using Force Spectrum Microscopy. Cell 2014, 158, 822 - 832. Publisher's Version 2014_cell_guo.pdf

doi: 10.1016/j.cell.2014.06.051

Datta, S. S. ; Abbaspourrad, A. ; Weitz, D. A. Expansion and rupture of charged microcapsules. Mater. Horiz. 2014, 1 92-95. Publisher's VersionAbstract

We study the deformations of pH-responsive spherical microcapsules - micrometer-scale liquid drops surrounded by thin{,} solid shells - under the influence of electrostatic forces. When exposed to a large concentration of NaOH{,} the microcapsules become highly charged{,} and expand isotropically. We find that the extent of this expansion can be understood by coupling electrostatics with shell theory; moreover{,} the expansion dynamics is well described by Darcy{'}s law for fluid flow through the microcapsule shell. Unexpectedly{,} however{,} below a threshold NaOH concentration{,} the microcapsules begin to disintegrate{,} and eventually rupture; they then expand non-uniformly{,} ultimately forming large{,} jellyfish-like structures. Our results highlight the fascinating range of behaviors exhibited by pH-responsive microcapsules{,} driven by the interplay between electrostatic and mechanical forces.

2014_materials_horizons_datta.pdf
Carroll, N. J. ; Jensen, K. H. ; Parsa, S. ; Holbrook, M. N. ; Weitz, D. A. Measurement of Flow Velocity and Inference of Liquid Viscosity in a Microfluidic Channel by Fluorescence Photobleaching. Langmuir 2014, 30, 4868-4874. Publisher's Version [PDF]
Datta, S. S. ; Dupin, J. - B. ; Weitz, D. A. Fluid breakup during simultaneous two-phase flow through a three-dimensional porous medium. Physics of Fluids 2014, 26, n/a–n/a. Publisher's Version [PDF]
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, n/a–n/a. Publisher's Version [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.

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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 Version [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 Version [PDF]
[*Equal contribution]
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 Version [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 Version [PDF]
[*Equal contribution]
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, n/a–n/a. 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.
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[*Equal contribution]
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 Version [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.

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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.

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