Publications by Year: 2018

2018
Wang, L. ; Xia, J. ; Li, J. ; Hagemann, T. L. ; Jones, J. R. ; Fraenkel, E. ; Weitz, D. A. ; Zhang, S. - C. ; Messing, A. ; Feany, M. B. Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease. Nat. Commun. 2018, 9 1899. Publisher's VersionAbstract
Glial cells have increasingly been implicated as active participants in the pathogenesis of neurological diseases, but critical pathways and mechanisms controlling glial function and secondary non-cell autonomous neuronal injury remain incompletely defined. Here we use models of Alexander disease, a severe brain disorder caused by gain-of-function mutations in GFAP, to demonstrate that misregulation of GFAP leads to activation of a mechanosensitive signaling cascade characterized by activation of the Hippo pathway and consequent increased expression of A-type lamin. Importantly, we use genetics to verify a functional role for dysregulated mechanotransduction signaling in promoting behavioral abnormalities and non-cell autonomous neurodegeneration. Further, we take cell biological and biophysical approaches to suggest that brain tissue stiffness is increased in Alexander disease. Our findings implicate altered mechanotransduction signaling as a key pathological cascade driving neuronal dysfunction and neurodegeneration in Alexander disease, and possibly also in other brain disorders characterized by gliosis.
wang2018.pdf
Zhang, L. ; Chen, K. ; Zhang, H. ; Pang, B. ; Choi, C. - H. ; Mao, A. S. ; Liao, H. ; Utech, S. ; Mooney, D. J. ; Wang, H. ; et al. Microfluidic Templated Multicompartment Microgels for 3D Encapsulation and Pairing of Single Cells. Small 2018, 14, 1-8. Publisher's VersionAbstract
Controlled encapsulation and pairing of single cells within a confined 3D matrix can enable the replication of the highly ordered cellular structure of human tissues. Microgels with independently controlled compartments that can encapsulate cells within separately confined hydrogel matrices would provide precise control over the route of pairing single cells. Here, a one‐step microfluidic method is presented to generate monodisperse multicompartment microgels that can be used as a 3D matrix to pair single cells in a highly biocompatible manner. A method is presented to induce microgels formation on chip, followed by direct extraction of the microgels from oil phase, thereby avoiding prolonged exposure of the microgels to the oil. It is further demonstrated that by entrapping stem cells with niche cells within separate but adjacent compartments of the microgels, it can create complex stem cell niche microenvironments in a controlled manner, which can serve as a useful tool for the study of cell–cell interactions. This microfluidic technique represents a significant step toward high‐throughput single cells encapsulation and pairing for the study of intercellular communications at single cell level, which is of significant importance for cell biology, stem cell therapy, and tissue engineering.
zhang2018.pdf
Atia, L. ; Bi, D. ; Sharma, Y. ; Mitchel, J. A. ; Gweon, B. ; Koehler, S. A. ; DeCamp, S. J. ; Lan, B. ; Kim, J. H. ; Hirsch, R. ; et al. Geometric constraints during epithelial jamming. Nature Physics 2018, 14, 613–620. Publisher's VersionAbstract
As an injury heals, an embryo develops or a carcinoma spreads, epithelial cells systematically change their shape. In each of these processes cell shape is studied extensively whereas variability of shape from cell to cell is regarded most often as biological noise. But where do cell shape and its variability come from? Here we report that cell shape and shape variability are mutually constrained through a relationship that is purely geometrical. That relationship is shown to govern processes as diverse as maturation of the pseudostratified bronchial epithelial layer cultured from non-asthmatic or asthmatic donors, and formation of the ventral furrow in the Drosophila embryo. Across these and other epithelial systems, shape variability collapses to a family of distributions that is common to all. That distribution, in turn, is accounted for by a mechanistic theory of cell–cell interaction, showing that cell shape becomes progressively less elongated and less variable as the layer becomes progressively more jammed. These findings suggest a connection between jamming and geometry that spans living organisms and inert jammed systems, and thus transcends system details. Although molecular events are needed for any complete theory of cell shape and cell packing, observations point to the hypothesis that jamming behaviour at larger scales of organization sets overriding geometric constraints.
lior2018.pdf
Edery, Y. ; Berg, S. ; Weitz, D. Surfactant Variations in Porous Media Localize Capillary Instabilities during Haines Jumps. Physical Review Letters 2018, 120. Publisher's VersionAbstract
We use confocal microscopy to measure velocity and interfacial tension between a trapped wetting phase with a surfactant and a flowing, invading nonwetting phase in a porous medium. We relate interfacial tension variations at the fluid-fluid interface to surfactant concentration and show that these variations localize the destabilization of capillary forces and lead to rapid local invasion of the nonwetting fluid, resulting in a Haines jump. These spatial variations in surfactant concentration are caused by velocity variations at the fluid-fluid interfaces and lead to localization of the Haines jumps even in otherwise very uniform pore structure and pressure conditions. Our results provide new insight into the nature of Haines jumps, one of the most ubiquitous and important instabilities in flow in porous media.
edery2018.pdf
Zhang, H. ; Zhu, Y. ; Qu, L. ; Wu, H. ; Kong, H. ; Yang, Z. ; Chen, D. ; Mäkilä, E. ; Salonen, J. ; Santos, H. A. ; et al. Gold nanorods conjugated porous silicon nanoparticles encapsulated in calcium alginate nano hydrogels using microemulsion templates. Nano Letters 2018, 18, 1448-1453. Publisher's VersionAbstract

Porous silicon nanoparticles (PSiNPs) and gold nanorods (AuNRs) can be used as biocompatible nanocarriers for delivery of therapeutics but undesired leakage makes them inefficient. By encapsulating the PSiNPs and AuNRs in a hydrogel shell, we create a biocompatible functional nanocarrier that enables sustained release of therapeutics. Here, we report the fabrication of AuNRs-conjugated PSi nanoparticles (AuNRsPSiNPs) through two-step chemical reaction for high-capacity loading of hydrophobic and hydrophilic therapeutics with photothermal property. Furthermore, using water-in-oil microemulsion templates, we encapsulate the AuNRsPSiNPs within a calcium alginate hydrogel nanoshell, creating a versatile biocompatible nanocarrier to codeliver therapeutics for biomedical applications. We find that the functionalized nanohydrogel effectively controls the release rate of the therapeutics while maintaining a high loading efficiency and tunable loading ratios. Notably, combinations of therapeutics coloaded in the functionalized nanohydrogels significantly enhance inhibition of multidrug resistance through synergism and promote faster cancer cell death when combined with photothermal therapy. Moreover, the AuNRs can mediate the conversion of near-infrared laser radiation into heat, increasing the release of therapeutics as well as thermally inducing cell damage to promote faster cancer cell death. Our AuNRsPSiNPs functionalized calcium alginate nanohydrogel holds great promise for photothermal combination therapy and other advanced biomedical applications.

zhang2018.pdf
Montessori, A. ; Lauricella, M. ; La Rocca, M. ; Succi, S. ; Stolovicki, E. ; Zibalt, R. ; Weitz, D. Regularized lattice Boltzmann multicomponent models for low capillary and Reynolds microfluidics flows. Computers & Fluids 2018, 167, 33-39. Publisher's VersionAbstract
We present a regularized version of the color gradient lattice Boltzmann (LB) scheme for the simulation of droplet formation in microfluidic devices of experimental relevance. The regularized version is shown to provide computationally efficient access to capillary number regimes relevant to droplet generation via microfluidic devices, such as flow-focusers and the more recent microfluidic step emulsifier devices.
montessori2018.pdf
Stolovicki, E. ; Ziblat, R. ; Weitz, D. A. Throughput enhancement of parallel step emulsifier devices by shear-free and efficient nozzle clearance. Lab on a Chip 2018, 18, 132-138. Publisher's VersionAbstract

Step emulsification is an attractive method for production of monodisperse drops. Its main advantage is the ability to parallelize many step emulsifier nozzles to achieve high production rates. However, step emulsification is sensitive to any obstructions at the nozzle exit. At high production rates, drops can accumulate at nozzle exits, disturb the formation of subsequent drops and impair monodispersity. As a result, parallelized step emulsifier devices typically do not work at maximum productivity. Here a design is introduced that parallelizes hundreds of step emulsifier nozzles, and effectively removes drops from the nozzle exits. The drop clearance is achieved by an open collecting channel, and is aided by buoyancy. Importantly, this clearance method avoids the use of a continuous phase flow for drop clearance and hence no shear is applied on the forming drops. The method works well for a wide range of drops, sizing from 30 to 1000 μm at production rates of 0.03 and 10 L per hour and achieved by 400 and 120 parallelized nozzles respectively.

stolovicki2018.pdf

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