Person: Mosadegh, Bobak
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Mosadegh
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Bobak
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Mosadegh, Bobak
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Publication Polymer-based mesh as supports for multi-layered 3D cell culture and assays(Elsevier BV, 2014) Simon, Karen Alambra; Park, Kyeng Min; Mosadegh, Bobak; Subramaniam, Anand; Mazzeo, Aaron D.; Ngo, Philip M.; Whitesides, GeorgeThree-dimensional (3D) culture systems can mimic certain aspects of the cellular microenvironment found in vivo, but generation, analysis and imaging of current model systems for 3D cellular constructs and tissues remain challenging. This work demonstrates a 3D culture system–Cells-in-Gels-in-Mesh (CiGiM)–that uses stacked sheets of polymer-based mesh to support cells embedded in gels to form tissue-like constructs; the stacked sheets can be disassembled by peeling the sheets apart to analyze cultured cells—layer-by-layer—within the construct. The mesh sheets leave openings large enough for light to pass through with minimal scattering, and thus allowing multiple options for analysis—(i) using straightforward analysis by optical light microscopy, (ii) by high-resolution analysis with fluorescence microscopy, or (iii) with a fluorescence gel scanner. The sheets can be patterned into separate zones with paraffin film-based decals, in order to conduct multiple experiments in parallel; the paraffin-based decal films also block lateral diffusion of oxygen effectively. CiGiM simplifies the generation and analysis of 3D culture without compromising throughput, and quality of the data collected: it is especially useful in experiments that require control of oxygen levels, and isolation of adjacent wells in a multi-zone format.Publication Multizone Paper Platform for 3D Cell Cultures(Public Library of Science (PLoS), 2011) Derda, Ratmir; Tang, Sindy K. Y.; Laromaine, Anna; Mosadegh, Bobak; Hong, Estrella; Mwangi, Martin; Mammoto, Akiko; Ingber, Donald; Whitesides, GeorgeIn vitro 3D culture is an important model for tissues in vivo. Cells in different locations of 3D tissues are physiologically different, because they are exposed to different concentrations of oxygen, nutrients, and signaling molecules, and to other environmental factors (temperature, mechanical stress, etc). The majority of high-throughput assays based on 3D cultures, however, can only detect the average behavior of cells in the whole 3D construct. Isolation of cells from specific regions of 3D cultures is possible, but relies on low-throughput techniques such as tissue sectioning and micromanipulation. Based on a procedure reported previously (“cells-in-gels-in-paper” or CiGiP), this paper describes a simple method for culture of arrays of thin planar sections of tissues, either alone or stacked to create more complex 3D tissue structures. This procedure starts with sheets of paper patterned with hydrophobic regions that form 96 hydrophilic zones. Serial spotting of cells suspended in extracellular matrix (ECM) gel onto the patterned paper creates an array of 200 micron-thick slabs of ECM gel (supported mechanically by cellulose fibers) containing cells. Stacking the sheets with zones aligned on top of one another assembles 96 3D multilayer constructs. De-stacking the layers of the 3D culture, by peeling apart the sheets of paper, “sections” all 96 cultures at once. It is, thus, simple to isolate 200-micron-thick cell-containing slabs from each 3D culture in the 96-zone array. Because the 3D cultures are assembled from multiple layers, the number of cells plated initially in each layer determines the spatial distribution of cells in the stacked 3D cultures. This capability made it possible to compare the growth of 3D tumor models of different spatial composition, and to examine the migration of cells in these structures.Publication Three-Dimensional Paper-Based Model for Cardiac Ischemia(Wiley-Blackwell, 2014) Mosadegh, Bobak; Dabiri, Borna; Lockett, Matthew; Derda, Ratmir; Campbell, Patrick; Parker, Kevin; Whitesides, GeorgeIn vitro models of ischemia have not historically recapitulated the cellular interactions and gradients of molecules that occur in a 3D tissue. This work demonstrates a paper-based 3D culture system that mimics some of the interactions that occur among populations of cells in the heart during ischemia. Multiple layers of paper containing cells, suspended in hydrogels, are stacked to form a layered 3D model of a tissue. Mass transport of oxygen and glucose into this 3D system can be modulated to induce an ischemic environment in the bottom layers of the stack. This ischemic stress induces cardiomyocytes at the bottom of the stack to secrete chemokines which subsequently trigger fibroblasts residing in adjacent layers to migrate toward the ischemic region. This work demonstrates the usefulness of patterned, stacked paper for performing in vitro mechanistic studies of cellular motility and viability within a model of the laminar ventricle tissue of the heart.Publication A Paper-Based Invasion Assay: Assessing Chemotaxis of Cancer Cells in Gradients of Oxygen(Elsevier BV, 2015) Mosadegh, Bobak; Lockett, Matthew; Minn, Kyaw Thu; Simon, Karen Alambra; Gilbert, Karl; Hillier, Shawn; Newsome, David; Li, Howard; Hall, Amy B.; Boucher, Diane M.; Eustace, Brenda K.; Whitesides, GeorgeThis work describes a 3D, paper-based assay that can isolate subpopulations of cells based on their invasiveness (i.e., distance migrated in a hydrogel) in a gradient of concentration of oxygen (O2). Layers of paper impregnated with a cell-compatible hydrogel are stacked and placed in a plastic holder to form the invasion assay. Stacking the layers of paper assembles them into 3D tissue-like constructs of defined thickness and composition. The plastic holder ensures the layers of paper are in conformal contact; this geometry allows the cells to migrate between adjacent layers through the embedded hydrogel. In most assays, the stack comprises a single layer of paper containing mammalian cells suspended in a hydrogel, sandwiched between multiple layers of paper containing only hydrogel (into which the cells migrate). Cells in the stack consume and produce small molecules; these molecules diffuse throughout the stack to generate gradients both in the stack, and between the stack and the bulk culture medium. Placing the cell-containing layer in different positions of the stack, or modifying the permeability of the holder to oxygen or proteins, alters the profile of the gradients within the stack. Physically separating the layers after culture isolates subpopulations of cells that migrated different distances, and enables their subsequent analysis or culture. Using this system, three independent cell lines derived from A549 cancer cells are shown to produce distinguishable migration behavior in a gradient of oxygen. This result is the first experimental demonstration that oxygen acts as a chemoattractant for cancer cells.Publication A 3D-printed, functionally graded soft robot powered by combustion(American Association for the Advancement of Science (AAAS), 2015) Bartlett, Nicholas; Tolley, M. T.; Overvelde, Johannes; Weaver, J; Mosadegh, Bobak; Bertoldi, Katia; Whitesides, George; Wood, RobertRoboticists have begun to design biologically inspired robots with soft or partially soft bodies, which have the potential to be more robust and adaptable, and safer for human interaction, than traditional rigid robots. However, key challenges in the design and manufacture of soft robots include the complex fabrication processes and the interfacing of soft and rigid components. We used multimaterial three-dimensional (3D) printing to manufacture a combustion-powered robot whose body transitions from a rigid core to a soft exterior. This stiffness gradient, spanning three orders of magnitude in modulus, enables reliable interfacing between rigid driving components (controller, battery, etc.) and the primarily soft body, and also enhances performance. Powered by the combustion of butane and oxygen, this robot is able to perform untethered jumping.Publication Buckling of Elastomeric Beams Enables Actuation of Soft Machines(Wiley-Blackwell, 2015) Yang, Dian; Mosadegh, Bobak; Ainla, Alar; Lee, Ben; Khashai, Fatemeh; Suo, Zhigang; Bertoldi, Katia; Whitesides, GeorgeSoft, pneumatic actuators that buckle when interior pressure is less than exterior provide a new mechanism of actuation. Upon application of negative pneumatic pressure, elastic beam elements in these actuators undergo reversible, cooperative collapse, and generate a rotational motion. These actuators are inexpensive to fabricate, lightweight, easy to control, and safe to operate. They can be used in devices that manipulate objects, locomote, or interact cooperatively with humans.Publication Disulfide-Based Diblock Copolymer Worm Gels: A Wholly-Synthetic Thermoreversible 3D Matrix for Sheet-Based Cultures(American Chemical Society (ACS), 2015) Simon, Karen Alambra; Warren, Nicholas J.; Mosadegh, Bobak; Mohammady, Marym R.; Whitesides, George; Armes, Steven P.It is well-known that 3D in vitro cell cultures provide a much better model than 2D cell cultures for understanding the in vivo microenvironment of cells. However, significant technical challenges in handling and analyzing 3D cell cultures remain, which currently limits their widespread application. Herein, we demonstrate the application of wholly synthetic thermoresponsive block copolymer worms in sheet-based 3D cell culture. These worms form a soft, free-standing gel reversibly at 20–37 °C, which can be rapidly converted into a free-flowing dispersion of spheres on cooling to 5 °C. Functionalization of the worms with disulfide groups was found to be essential for ensuring sufficient mechanical stability of these hydrogels to enable long-term cell culture. These disulfide groups are conveniently introduced via statistical copolymerization of a disulfide-based dimethacrylate under conditions that favor intramolecular cyclization and subsequent thiol/disulfide exchange leads to the formation of reversible covalent bonds between adjacent worms within the gel. This new approach enables cells to be embedded within micrometer-thick slabs of gel with good viability, permits cell culture for at least 12 days, and facilitates recovery of viable cells from the gel simply by incubating the culture in buffer at 4 °C (thus, avoiding the enzymatic degradation required for cell harvesting when using commercial protein-based gels, such as Matrigel).Publication Pneumatic Networks for Soft Robotics that Actuate Rapidly(Wiley-Blackwell, 2014) Mosadegh, Bobak; Polygerinos, Panagiotis; Keplinger, Christoph; Wennstedt, Sophia; Shepherd, Robert F.; Gupta, Unmukt; Shim, Jongmin; Bertoldi, Katia; Walsh, Conor; Whitesides, GeorgeSoft robots actuated by pressurization and inflation of a pneumatic network (a “pneu-net”) of small channels in elastomeric materials are appealing for their ability to produce sophisticated motions with simple controls. Although current designs of pneu-nets achieve motion with large amplitudes, they do so relatively slowly (that is, over seconds). This paper describes a new design for pneu-nets that reduces the amount of gas that must be transported for inflation of the pneu-net, and thus increases its speed of actuation. A simple actuator can bend from a linear shape to a quasi-circular shape in 50 milliseconds when pressurized at ΔP = 345 kPa. At high rates of pressurization and inflation, the path along which the actuator bends depends on this rate. When inflated fully, the channels and chambers of this new pneu-net design experience only one-tenth the change in volume of that required for a motion of equal amplitude using the previous design. This small change in volume requires comparably low levels of strain in the material at maximum amplitudes of actuation, and commensurately low rates of fatigue and failure. This actuator can operate over a million cycles without significant degradation of performance. This design for soft robotic actuators combines high rates of actuation with high reliability of the actuator, and opens new areas of application for them.Publication Metabolic response of lung cancer cells to radiation in a paper-based 3D cell culture system(Elsevier BV, 2016) Simon, Karen Alambra; Mosadegh, Bobak; Minn, Kyaw Thu; Lockett, Matthew; Mohammady, Marym R.; Boucher, Diane M.; Hall, Amy B.; Hillier, Shawn M.; Udagawa, Taturo; Eustace, Brenda K.; Whitesides, GeorgeThis work demonstrates the application of a 3D culture system - Cells-in-Gels-in-Paper (CiGiP) - in evaluating the metabolic response of lung cancer cells to ionizing radiation. The 3D tissue-like construct - prepared by stacking multiple sheets of paper containing cell-embedded hydrogels - generates a gradient of oxygen and nutrients that decreases monotonically in the stack. Separating the layers of the stack after exposure enabled analysis of the cellular response to radiation as a function of oxygen and nutrient availability; this availability is dictated by the distance between the cells and the source of oxygenated medium. As the distance between the cells and source of oxygenated media increased, cells show increased levels of hypoxia-inducible factor 1-alpha, decreased proliferation, and reduced sensitivity to ionizing radiation. Each of these cellular responses are characteristic of cancer cells observed in solid tumors. With this setup we were able to differentiate three isogenic variants of A549 cells based on their metabolic radiosensitivity; these three variants have known differences in their metastatic behavior in vivo. This system can, therefore, capture some aspects of radiosensitivity of populations of cancer cells related to mass-transport phenomenon, carry out systematic studies of radiation response in vitro that decouple effects from migration and proliferation of cells, and regulate the exposure of oxygen to subpopulations of cells in a tissue-like construct either before or after irradiation.Publication Paper-Based Electrical Respiration Sensor(Wiley-Blackwell, 2016) Guder, Firat; Ainla, Alar; Redston, Julia; Mosadegh, Bobak; Glavan, Ana; Martin, T. J.; Whitesides, GeorgeCurrent methods of monitoring breathing require cumbersome, inconvenient, and often expensive devices; this requirement sets practical limitations on the frequency and duration of measurements. This article describes a paper-based moisture sensor that uses the hygroscopic character of paper (i.e. the ability of paper to adsorb water reversibly from the surrounding environment) to measure patterns and rate of respiration by converting the changes in humidity caused by cycles of inhalation and exhalation to electrical signals. The changing level of humidity that occurs in a cycle causes a corresponding change in the ionic conductivity of the sensor, which can be measured electrically. By combining the paper sensor with conventional electronics, data concerning respiration can be transmitted to a nearby smartphone or tablet computer for post-processing, and subsequently to a cloud server. This means of sensing provides a new, practical method of recording and analyzing patterns of breathing.