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157. Neutrophil swarming delays the growth of clusters of pathogenic fungi.

Author

Alex, Hopke, Scherer, Allison, Kreuzburg, Samantha, Abers, Michael S., Zerbe, Christa S., Dinauer, Mary C., Mansour, Michael K., and Irimia, Daniel

Subjects
NEUTROPHILS, PATHOGENIC fungi, CHRONIC granulomatous disease, NADPH oxidase, FUNGAL growth, CHEMICAL inhibitors
Abstract

Neutrophils employ several mechanisms to restrict fungi, including the action of enzymes such as myeloperoxidase (MPO) or NADPH oxidase, and the release of neutrophil extracellular traps (NETs). Moreover, they cooperate, forming "swarms" to attack fungi that are larger than individual neutrophils. Here, we designed an assay for studying how these mechanisms work together and contribute to neutrophil's ability to contain clusters of live Candida. We find that neutrophil swarming over Candida clusters delays germination through the action of MPO and NADPH oxidase, and restricts fungal growth through NET release within the swarm. In comparison with neutrophils from healthy subjects, those from patients with chronic granulomatous disease produce larger swarms against Candida, but their release of NETs is delayed, resulting in impaired control of fungal growth. We also show that granulocyte colony-stimulating factors (GCSF and GM-CSF) enhance swarming and neutrophil ability to restrict fungal growth, even during treatment with chemical inhibitors that disrupt neutrophil function. Neutrophils employ several mechanisms to control the growth of fungi, including enzymes, reactive oxygen species, extracellular traps, and formation of "swarms". Here, Hopke et al. study how the different mechanisms work together, using an in vitro assay with human neutrophils and clusters of live Candida cells. [ABSTRACT FROM AUTHOR]

Published
2020
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159. Sepsis is associated with reduced spontaneous neutrophil migration velocity in human adults

Author

Raymond, Steven L., primary, Hawkins, Russell B., additional, Stortz, Julie A., additional, Murphy, Tyler J., additional, Ungaro, Ricardo, additional, Dirain, Marvin L., additional, Nacionales, Dina C., additional, Hollen, McKenzie K., additional, Rincon, Jaimar C., additional, Larson, Shawn D., additional, Brakenridge, Scott C., additional, Moore, Frederick A., additional, Irimia, Daniel, additional, Efron, Phil A., additional, and Moldawer, Lyle L., additional

Published
2018
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161. Trapped Chromatin Fibers Damage Flowing Red Blood Cells

Author

Roushan, Maedeh, primary, Jorfi, Mehdi, additional, Mishra, Avanish, additional, Wong, Keith H. K., additional, Jorgensen, Julianne, additional, Ell, Eric, additional, Markmann, James F., additional, Lee, Jarone, additional, and Irimia, Daniel, additional

Published
2018
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162. Tau reduction in the presence of amyloid-β prevents tau pathology and neuronal death in vivo

Author

DeVos, Sarah L, primary, Corjuc, Bianca T, additional, Commins, Caitlin, additional, Dujardin, Simon, additional, Bannon, Riley N, additional, Corjuc, Diana, additional, Moore, Benjamin D, additional, Bennett, Rachel E, additional, Jorfi, Mehdi, additional, Gonzales, Jose A, additional, Dooley, Patrick M, additional, Roe, Allyson D, additional, Pitstick, Rose, additional, Irimia, Daniel, additional, Frosch, Matthew P, additional, Carlson, George A, additional, and Hyman, Bradley T, additional

Published
2018
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163. Toward elucidating the mechanism of femtosecond pulse shaping control in photodynamics of molecules by velocity map photoelectron and ion imaging.

Author

Irimia, Daniel and Janssen, Maurice H. M.

Subjects
*FEMTOSECOND lasers research, *POLYATOMIC molecules, *PHOTOELECTRONS, *IONIZATION (Atomic physics), *MASS spectrometry, *ANISOTROPY, *PHYSICS research
Abstract

The control of photofragmentation and ionization in a polyatomic molecule has been studied by femtosecond chirped laser pulse excitation and velocity map photoelectron and ion imaging. The experiments aimed at controlling and investigating the photodynamics in CH2BrCl using tunable chirped femtosecond pulses in the visible wavelength region 509–540 nm at maximum intensities of about 4×1013 W/cm2. We observe that the time-of-flight mass spectra as well as the photoelectron images can be strongly modified by manipulating the chirp parameter of ultrashort laser pulses. Specifically, a strong enhancement of the CH2Cl+/CH2BrCl+ ion ratio by a factor of five and changes in the photoelectron spectra are observed for positively chirped pulses centered near 520 nm. These changes are only observed within a narrow window of wavelengths around 520 nm and only for positively chirped pulses. From the combination of the photoelectron spectra and the ion recoil energy of the CH2Cl+ fragment we can deduce that the parent ionization and fragmentation is induced by a multiphoton excitation with five photons. The photoelectron images and the fragment ion images also provide the anisotropy (β-parameter) of the various electron bands and fragment ions. We conclude that multiphoton excitation of the highest occupied 22a′ and 8a″ CH2BrCl molecular orbitals of Br-character are both involved in the five-photon ionization, however, only excitation of the 22a′ orbital appears to be (mostly) involved in the chirped control dynamics leading to enhanced fragmentation to CH2Cl+(X A′)+Br(2P3/2). We propose that a wavepacket following or a time-delay resonance mechanism between the two-photon excited nx(Br,22a′)→(2A′) repulsive surface and the three-photon near-resonant nx(Br,22a′)→Rydberg(A′) state of the neutral CH2BrCl molecule is responsible for the enhanced excitation of the nx(Br,22a′) molecular orbital with up-chirped pulses. This leads to enhanced ionization to a configuration in the CH2BrCl+(X A′) continuum just above the dissociation limit of the CH2Cl++Br(2P3/2) channel, resulting in enhanced fragmentation. [ABSTRACT FROM AUTHOR]

Published
2010
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164. Desiccation kinetics of biopreservation solutions in microchannels.

Author

Aksan, Alptekin, Irimia, Daniel, Xiaoming He, and Toner, Mehmet

Subjects
*PHASE transitions, *MICROFLUIDICS, *GLASS transition temperature, *TRANSITION temperature, *SPATIAL variation, *VISCOSITY, *SOLUTION (Chemistry)
Abstract

A microfluidic device was utilized to measure the viscosity gradients formed in carbohydrate solutions of biological significance during desiccation and skin formation. A complementary numerical model employed the free volume theory to predict the concentration-dependent diffusion coefficients and viscosity gradients in concentrated solutions. It was established that the glassy skin formation at the gas-liquid interface played a key role in water entrapment and the formation and persistence of very steep concentration and viscosity gradients in the desiccating solutions. The results of this study highlighted an important phenomenon that should be accounted for during isothermal drying of glass-forming solutions: solutions with high glass transition temperatures, inevitably, dry heterogeneously. In the final product, there are significant spatial variations in water and solute content affecting the storage stability. [ABSTRACT FROM AUTHOR]

Published
2006
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166. A genome-wide RNAi screen identifies multiple RSK-dependent regulators of cell migration

Author

Smolen, Gromoslaw A., Zhang, Jianmin, Zubrowski, Matthew J., Edelman, Elena J., Luo, Biao, Min Yu, Ng, Lydia W., Scherber, Cally M., Schott, Benjamin J., Ramaswamy, Sridhar, Irimia, Daniel, Root, David E., and Haber, Daniel A.

Subjects
Cell migration -- Analysis, Epithelial cells -- Physiological aspects, Biological sciences
Published
2010

168. NETRIN-1 AUGMENTS CHEMOKINESIS IN CD4+ T CELLS IN VITRO AND ELICITS A PROINFLAMMATORY RESPONSE IN VIVO1

Author

Boneschansker, Leo, Nakayama, Hironao, Eisenga, Michele, Wedel, Johannes, Klagsbrun, Michael, Irimia, Daniel, and Briscoe, David M

Subjects
CD4-Positive T-Lymphocytes, Tumor Suppressor Proteins, Blotting, Western, Fluorescent Antibody Technique, Receptors, Cell Surface, Mice, SCID, In Vitro Techniques, Microfluidic Analytical Techniques, Netrin-1, Flow Cytometry, Real-Time Polymerase Chain Reaction, Article, Chemotaxis, Leukocyte, Mice, Animals, Humans, Nerve Growth Factors, Netrin Receptors, Cells, Cultured
Abstract

Netrin-1 is a neuronal guidance cue that regulates cellular activation, migration, and cytoskeleton rearrangement in multiple cell types. It is a chemotropic protein that is expressed within tissues and elicits both attractive and repulsive migratory responses. Netrin-1 has recently been found to modulate the immune response via the inhibition of neutrophil and macrophage migration. However, the ability of Netrin-1 to interact with lymphocytes and its in-depth effects on leukocyte migration are poorly understood. In this study, we profiled the mRNA and protein expression of known Netrin-1 receptors on human CD4(+) T cells. Neogenin, uncoordinated-5 (UNC5)A, and UNC5B were expressed at low levels in unstimulated cells, but they increased following mitogen-dependent activation. By immunofluorescence, we observed a cytoplasmic staining pattern of neogenin and UNC5A/B that also increased following activation. Using a novel microfluidic assay, we found that Netrin-1 stimulated bidirectional migration and enhanced the size of migratory subpopulations of mitogen-activated CD4(+) T cells, but it had no demonstrable effects on the migration of purified CD4(+)CD25(+)CD127(dim) T regulatory cells. Furthermore, using a short hairpin RNA knockdown approach, we observed that the promigratory effects of Netrin-1 on T effectors is dependent on its interactions with neogenin. In the humanized SCID mouse, local injection of Netrin-1 into skin enhanced inflammation and the number of neogenin-expressing CD3(+) T cell infiltrates. Neogenin was also observed on CD3(+) T cell infiltrates within human cardiac allograft biopsies with evidence of rejection. Collectively, our findings demonstrate that Netrin-1/neogenin interactions augment CD4(+) T cell chemokinesis and promote cellular infiltration in association with acute inflammation in vivo.

Published
2016

177. Resolvin D2 Limits Secondary Tissue Necrosis After Burn Wounds in Rats

Author

Inoue, Yoshitaka, primary, Liu, Yuk Ming, additional, Otawara, Masayuki, additional, Chico Calero, Isabel, additional, Stephanie Nam, Ahhyun, additional, Yu, Yong-Ming, additional, Chang, Philip, additional, Butler, Kathryn L., additional, Nazarian, Rosalynn M., additional, Goverman, Jeremy, additional, Vakoc, Benjamin J., additional, and Irimia, Daniel, additional

Published
2017
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178. Preservative solution that stabilizes erythrocyte morphology and leukocyte viability under ambient conditions

Author

Sandlin, Rebecca D., primary, Wong, Keith H. K., additional, Boneschansker, Leo, additional, Carey, Thomas R., additional, Miller, Kathleen L., additional, Rose, Gregory, additional, Haber, Daniel A., additional, Maheswaran, Shyamala, additional, Irimia, Daniel, additional, Stott, Shannon L., additional, and Toner, Mehmet, additional

Published
2017
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184. Synthesis of Cell-Adhesive Anisotropic Multifunctional Particles by Stop Flow Lithography and Streptavidin–Biotin Interactions

Author

Massachusetts Institute of Technology. Department of Chemical Engineering, Doyle, Patrick S, Kim, Jae Jung, Cho, Hansang, Lim, Eugene, Irimia, Daniel, Bong, Ki Wan, Massachusetts Institute of Technology. Department of Chemical Engineering, Doyle, Patrick S, Kim, Jae Jung, Cho, Hansang, Lim, Eugene, Irimia, Daniel, and Bong, Ki Wan

Abstract

Cell-adhesive particles are of significant interest in biotechnology, the bioengineering of complex tissues, and biomedical research. Their applications range from platforms to increase the efficiency of anchorage-dependent cell culture to building blocks to loading cells in heterogeneous structures to clonal-population growth monitoring to cell sorting. Although useful, currently available cell-adhesive particles can accommodate only homogeneous cell culture. Here, we report the design of anisotropic hydrogel microparticles with tunable cell-adhesive regions as first step toward micropatterned cell cultures on particles. We employed stop flow lithography (SFL), the coupling reaction between amine and N-hydroxysuccinimide (NHS) and streptavidin–biotin chemistry to adjust the localization of conjugated collagen and poly-l-lysine on the surface of microscale particles. Using the new particles, we demonstrate the attachment and formation of tight junctions between brain endothelial cells. We also demonstrate the geometric patterning of breast cancer cells on particles with heterogeneous collagen coatings. This new approach avoids the exposure of cells to potentially toxic photoinitiators and ultraviolet light and decouples in time the microparticle synthesis and the cell culture steps to take advantage of the most recent advances in cell patterning available for traditional culture substrates., National Institutes of Health (U.S.) (GM092804), National Science Foundation (U.S.) (CMMI-1120724 and DMR-1006147), Samsung Scholarship Foundation

Published
2017

185. Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Division of Comparative Medicine, Frydman, Galit, Ellett, Felix, Jorgensen, Julianne, Jones, Caroline N., Irimia, Daniel, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Division of Comparative Medicine, Frydman, Galit, Ellett, Felix, Jorgensen, Julianne, Jones, Caroline N., and Irimia, Daniel

Abstract

Invasive aspergillosis (IA), primarily caused by Aspergillus fumigatus, is an opportunistic fungal infection predominantly affecting immunocompromised and neutropenic patients that is difficult to treat and results in high mortality. Investigations of neutrophil-hypha interaction in vitro and in animal models of IA are limited by lack of temporal and spatial control over interactions. This study presents a new approach for studying neutrophil-hypha interaction at single cell resolution over time, which revealed an evasive fungal behavior triggered by interaction with neutrophils: Interacting hyphae performed de novo tip formation to generate new hyphal branches, allowing the fungi to avoid the interaction point and continue invasive growth. Induction of this mechanism was independent of neutrophil NADPH oxidase activity and neutrophil extracellular trap (NET) formation, but could be phenocopied by iron chelation and mechanical or physiological stalling of hyphal tip extension. The consequence of branch induction upon interaction outcome depends on the number and activity of neutrophils available: In the presence of sufficient neutrophils branching makes hyphae more vulnerable to destruction, while in the presence of limited neutrophils the interaction increases the number of hyphal tips, potentially making the infection more aggressive. This has direct implications for infections in neutrophil-deficient patients and opens new avenues for treatments targeting fungal branching., United States. National Institutes of Health (EB002503), United States. National Institutes of Health (GM092804)

Published
2017

186. Porous microwells for geometry-selective, large-scale microparticle arrays

Author

Massachusetts Institute of Technology. Department of Chemical Engineering, Kim, Jae Jung, Doyle, Patrick S, Bong, Ki Wan, Reátegui, Eduardo, Irimia, Daniel, Massachusetts Institute of Technology. Department of Chemical Engineering, Kim, Jae Jung, Doyle, Patrick S, Bong, Ki Wan, Reátegui, Eduardo, and Irimia, Daniel

Abstract

Large-scale microparticle arrays (LSMAs) are key for material science and bioengineering applications. However, previous approaches suffer from trade-offs between scalability, precision, specificity and versatility. Here, we present a porous microwell-based approach to create large-scale microparticle arrays with complex motifs. Microparticles are guided to and pushed into microwells by fluid flow through small open pores at the bottom of the porous well arrays. A scaling theory allows for the rational design of LSMAs to sort and array particles on the basis of their size, shape, or modulus. Sequential particle assembly allows for proximal and nested particle arrangements, as well as particle recollection and pattern transfer. We demonstrate the capabilities of the approach by means of three applications: high-throughput single-cell arrays; microenvironment fabrication for neutrophil chemotaxis; and complex, covert tags by the transfer of an upconversion nanocrystal-laden LSMA., National Science Foundation (U.S.) (Grant CMMI-1120724), Samsung Scholarship Foundation, National Institutes of Health (U.S.) (Grant GM092804), National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Award DMR-1419807)

Published
2017

190. Neuronal uptake and propagation of a rare phosphorylated high-molecular-weight tau derived from Alzheimer's disease brain

Author

Takeda, Shuko, Wegmann, Susanne, Cho, Hansang, DeVos, Sarah L., Commins, Caitlin, Roe, Allyson D., Nicholls, Samantha B., Carlson, George A., Pitstick, Rose, Nobuhara, Chloe K., Costantino, Isabel, Frosch, Matthew P., Müller, Daniel J., Irimia, Daniel, and Hyman, Bradley T.

Subjects
mental disorders
Abstract

Tau pathology is known to spread in a hierarchical pattern in Alzheimer’s disease (AD) brain during disease progression, likely by trans-synaptic tau transfer between neurons. However, the tau species involved in inter-neuron propagation remains unclear. To identify tau species responsible for propagation, we examined uptake and propagation properties of different tau species derived from postmortem cortical extracts and brain interstitial fluid of tau-transgenic mice, as well as human AD cortices. Here we show that PBS-soluble phosphorylated high-molecular-weight (HMW) tau, though very low in abundance, is taken up, axonally transported, and passed on to synaptically connected neurons. Our findings suggest that a rare species of soluble phosphorylated HMW tau is the endogenous form of tau involved in propagation and could be a target for therapeutic intervention and biomarker development. ISSN:2041-1723

Published
2015

191. Unified framework for laser-induced transient bubble dynamics within microchannels.

Author

Nagalingam, Nagaraj, Korede, Vikram, Irimia, Daniel, Westerweel, Jerry, Padding, Johan T., Hartkamp, Remco, and Eral, Hüseyin Burak

Subjects
*TRANSIENTS (Dynamics), *BUBBLE dynamics, *BOUNDARY layer separation, *PULSATILE flow, *CAVITATION, *REYNOLDS number, *JAHN-Teller effect
Abstract

Oscillatory flow in confined spaces is central to understanding physiological flows and rational design of synthetic periodic-actuation based micromachines. Using theory and experiments on oscillating flows generated through a laser-induced cavitation bubble, we associate the dynamic bubble size (fluid velocity) and bubble lifetime to the laser energy supplied—a control parameter in experiments. Employing different channel cross-section shapes, sizes and lengths, we demonstrate the characteristic scales for velocity, time and energy to depend solely on the channel geometry. Contrary to the generally assumed absence of instability in low Reynolds number flows ( < 1000 ), we report a momentary flow distortion that originates due to the boundary layer separation near channel walls during flow deceleration. The emergence of distorted laminar states is characterized using two stages. First the conditions for the onset of instabilities is analyzed using the Reynolds number and Womersley number for oscillating flows. Second the growth and the ability of an instability to prevail is analyzed using the convective time scale of the flow. Our findings inform rational design of microsystems leveraging pulsatile flows via cavitation-powered microactuation. [ABSTRACT FROM AUTHOR]

Published
2024
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196. Secondary Wound Necrosis is Suppressed by Resolvin D2

Author

Liu, Yuk M., primary, Inoue, Yoshitaka, additional, Otawara, Masayuki, additional, Yu, Yong-Ming, additional, Chang, Philip H., additional, Tompkins, Ronald G., additional, Vakoc, Benjamin, additional, Goverman, Jeremy, additional, and Irimia, Daniel, additional

Published
2016
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200. A Worldwide Competition to Compare the Speed and Chemotactic Accuracy of Neutrophil-Like Cells

Author

Skoge, Monica, primary, Wong, Elisabeth, additional, Hamza, Bashar, additional, Bae, Albert, additional, Martel, Joseph, additional, Kataria, Rama, additional, Keizer-Gunnink, Ineke, additional, Kortholt, Arjan, additional, Van Haastert, Peter J. M., additional, Charras, Guillaume, additional, Janetopoulos, Christopher, additional, and Irimia, Daniel, additional

Published
2016
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