Publications by Year: 2015

2015
Park, J. ; Elmlund, H. ; Ercius, P. ; Yuk, J. M. ; Limmer, D. T. ; Chen, Q. ; Kim, K. ; Han, S. H. ; Weitz, D. A. ; Zettl, A. ; et al. 3D structure of individual nanocrystals in solution by electron microscopy. Science 2015, 349, 290-295. Publisher's VersionAbstract

Knowledge about the synthesis, growth mechanisms, and physical properties of colloidal nanoparticles has been limited by technical impediments. We introduce a method for determining three-dimensional (3D) structures of individual nanoparticles in solution. We combine a graphene liquid cell, high-resolution transmission electron microscopy, a direct electron detector, and an algorithm for single-particle 3D reconstruction originally developed for analysis of biological molecules. This method yielded two 3D structures of individual platinum nanocrystals at near-atomic resolution. Because our method derives the 3D structure from images of individual nanoparticles rotating freely in solution, it enables the analysis of heterogeneous populations of potentially unordered nanoparticles that are synthesized in solution, thereby providing a means to understand the structure and stability of defects at the nanoscale.

2015_science_park.pdf
Park, J. ; Park, H. ; Ercius, P. ; Pegoraro, A. F. ; Xu, C. ; Kim, J. W. ; Han, S. H. ; Weitz, D. A. Direct Observation of Wet Biological Samples by Graphene Liquid Cell Transmission Electron Microscopy. Nano Letters 2015, 15, 4737-4744. Publisher's VersionAbstract

Recent development of liquid phase transmission electron microscopy (TEM) enables the study of specimens in wet ambient conditions within a liquid cell; however, direct structural observation of biological samples in their native solution using TEM is challenging since low-mass biomaterials embedded in a thick liquid layer of the host cell demonstrate low contrast. Furthermore, the integrity of delicate wet samples is easily compromised during typical sample preparation and TEM imaging. To overcome these limitations, we introduce a graphene liquid cell (GLC) using multilayer graphene sheets to reliably encapsulate and preserve biological samples in a liquid for TEM observation. We achieve nanometer scale spatial resolution with high contrast using low-dose TEM at room temperature, and we use the GLC to directly observe the structure of influenza viruses in their native buffer solution at room temperature. The GLC is further extended to investigate whole cells in wet conditions using TEM. We also demonstrate the potential of the GLC for correlative studies by TEM and fluorescence light microscopy imaging.

2015_nanoletter_park.pdf
Rotem, A. ; Ram, O. ; Shoresh, N. ; Sperling, R. A. ; Schnall-Levin, M. ; Zhang, H. ; Basu, A. ; Bernstein, B. E. ; Weitz, D. A. High-Throughput Single-Cell Labeling (Hi-SCL) for RNA-Seq Using Drop-Based Microfluidics. PLoS ONE 2015, 10, e0116328. Publisher's VersionAbstract

The importance of single-cell level data is increasingly appreciated, and significant advances in this direction have been made in recent years. Common to these technologies is the need to physically segregate individual cells into containers, such as wells or chambers of a micro-fluidics chip. High-throughput Single-Cell Labeling (Hi-SCL) in drops is a novel method that uses drop-based libraries of oligonucleotide barcodes to index individual cells in a population. The use of drops as containers, and a microfluidics platform to manipulate them en-masse, yields a highly scalable methodological framework. Once tagged, labeled molecules from different cells may be mixed without losing the cell-of-origin information. Here we demonstrate an application of the method for generating RNA-sequencing data for multiple individual cells within a population. Barcoded oligonucleotides are used to prime cDNA synthesis within drops. Barcoded cDNAs are then combined and subjected to second generation sequencing. The data are deconvoluted based on the barcodes, yielding single-cell mRNA expression data. In a proof-of-concept set of experiments we show that this method yields data comparable to other existing methods, but with unique potential for assaying very large numbers of cells.

2015_plosone_rotem.pdf
Jensen, M. H. ; Morris, E. J. ; Weitz, D. A. Mechanics and dynamics of reconstituted cytoskeletal systems. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 2015, 1853, 3038-3042. Publisher's VersionAbstract

The intracellular cytoskeleton is an active dynamic network of filaments and associated binding proteins that control key cellular properties, such as cell shape and mechanics. Due to the inherent complexity of the cell, reconstituted model systems have been successfully employed to gain an understanding of the fundamental physics governing cytoskeletal processes. Here, we review recent advances and key aspects of these reconstituted systems. We focus on the importance of assembly kinetics and dynamic arrest in determining network mechanics, and highlight novel emergent behavior occurring through interactions between cytoskeletal components in more complex networks incorporating multiple biopolymers and molecular motors.

2015_bba_jensen.pdf
Akamatsu, K. ; Kanasugi, S. ; Nakao, S. -ichi; Weitz, D. A. Membrane-Integrated Glass Capillary Device for Preparing Small-Sized Water-in-Oil-in-Water Emulsion Droplets. Langmuir 2015, 31, 7166-7172. Publisher's VersionAbstract

In this study, a membrane-integrated glass capillary device for preparing small-sized water-in-oil-in-water (W/O/W) emulsion droplets is demonstrated. The concept of integrating microfluidics to prepare precise structure-controlled double emulsion droplets with the membrane emulsification technique provides a simple method for preparing small-sized and structure-controlled double emulsion droplets. The most important feature of the integrated device is the ability to decrease droplet size when the emulsion droplets generated at the capillary pass through the membrane. At the same time, most of the oil shell layer is stripped away and the resultant double emulsion droplets have thin shells. It is also demonstrated that the sizes of the resultant double emulsion droplets are greatly affected by both the double emulsion droplet flux through membranes and membrane pore size; when the flux is increased and membrane pore size is decreased, the generated W/O/W emulsion droplets are smaller than the original. In situ observation of the permeation behavior of the W/O/W emulsion droplets through membranes using a high-speed camera demonstrates (1) the stripping of the middle oil phase, (2) the division of the double emulsion droplets to generate two or more droplets with smaller size, and (3) the collapse of the double emulsion droplets. The first phenomenon results in a thinner oil shell, and the second division phenomenon produces double emulsion droplets that are smaller than the original.

2015_langmuir_akamatsu.pdf
Kong, F. ; Zhang, X. ; Zhang, H. ; Qu, X. ; Chen, D. ; Servos, M. ; Mäkilä, E. ; Salonen, J. ; Santos, H. A. ; Hai, M. ; et al. Inhibition of Multidrug Resistance of Cancer Cells by Co-Delivery of DNA Nanostructures and Drugs Using Porous Silicon Nanoparticles@Giant Liposomes. Advanced Functional Materials 2015, 25, 3330–3340. Publisher's VersionAbstract

Biocompatible, multifunctional, stimuli responsive, and high drug loading capacity are key factors for the new generation of drug delivery platforms. However, it is extremely challenging to create such a platform that inherits all these advanced properties in a single carrier. Herein, porous silicon nanoparticles (PSi NPs) and giant liposomes are assembled on a microfluidic chip as an advanced nano‐in‐micro platform (PSi NPs@giant liposomes), which can co‐load and co‐deliver hydrophilic and hydrophobic drugs combined with synthesized DNA nanostructures, short gold nanorods, and magnetic nanoparticles. The PSi NPs@giant liposomes with photothermal and magnetic responsiveness show good biocompatibility, high loading capacity, and controllable release. The hydrophilic thermal oxidized PSi NPs encapsulate hydrophobic therapeutics within the hydrophilic core of the giant liposomes, endowing high therapeutics loading capacity with tuneable ratio and controllable release. It is demonstrated that the DAO‐E A adfm201500594-math-0001 DNA nanostructures have synergism with drugs and importantly they contribute to the significant enhancement of cell death to doxorubicin‐resistant MCF‐7/DOX cells, overcoming the multidrug resistance in the cancer cells. Therefore, the PSi NPs@giant liposomes nano‐in‐micro platform hold great potential for a cocktail delivery of drugs and DNA nanostructures for effective cancer therapy, controllable drug release with tuneable therapeutics ratio, and both photothermal and magnetic dual responsiveness.

2015_adfm_kong.pdf
Fodor, É. ; Guo, M. ; Gov, N. S. ; Visco, P. ; Weitz, D. A. ; van Wijland, F. Activity-driven fluctuations in living cells. EPL (Europhysics Letters) 2015, 110, 48005. Publisher's VersionAbstract

We propose a model for the dynamics of a probe embedded in a living cell, where both thermal fluctuations and nonequilibrium activity coexist. The model is based on a confining harmonic potential describing the elastic cytoskeletal matrix, which undergoes random active hops as a result of the nonequilibrium rearrangements within the cell. We describe the probe's statistics and we bring forth quantities affected by the nonequilibrium activity. We find an excellent agreement between the predictions of our model and experimental results for tracers inside living cells. Finally, we exploit our model to arrive at quantitative predictions for the parameters characterizing nonequilibrium activity, such as the typical time scale of the activity and the amplitude of the active fluctuations.

2015_epl_fodor.pdf
Ehrlicher, A. J. ; Krishnan, R. ; Guo, M. ; Bidan, C. M. ; Weitz, D. A. ; Pollak, M. R. Alpha-actinin binding kinetics modulate cellular dynamics and force generation. Proceedings of the National Academy of Sciences 2015, 112, 6619-6624. Publisher's VersionAbstract

The actin cytoskeleton is a key element of cell structure and movement whose properties are determined by a host of accessory proteins. Actin cross-linking proteins create a connected network from individual actin filaments, and though the mechanical effects of cross-linker binding affinity on actin networks have been investigated in reconstituted systems, their impact on cellular forces is unknown. Here we show that the binding affinity of the actin cross-linker α-actinin 4 (ACTN4) in cells modulates cytoplasmic mobility, cellular movement, and traction forces. Using fluorescence recovery after photobleaching, we show that an ACTN4 mutation that causes human kidney disease roughly triples the wild-type binding affinity of ACTN4 to F-actin in cells, increasing the dissociation time from 29 ± 13 to 86 ± 29 s. This increased affinity creates a less dynamic cytoplasm, as demonstrated by reduced intracellular microsphere movement, and an approximate halving of cell speed. Surprisingly, these less motile cells generate larger forces. Using traction force microscopy, we show that increased binding affinity of ACTN4 increases the average contractile stress (from 1.8 ± 0.7 to 4.7 ± 0.5 kPa), and the average strain energy (0.4 ± 0.2 to 2.1 ± 0.4 pJ). We speculate that these changes may be explained by an increased solid-like nature of the cytoskeleton, where myosin activity is more partitioned into tension and less is dissipated through filament sliding. These findings demonstrate the impact of cross-linker point mutations on cell dynamics and forces, and suggest mechanisms by which such physical defects lead to human disease.

2015_pnas_ehrlicher.pdf
Hackelbusch, S. ; Rossow, T. ; Steinhilber, D. ; Weitz, D. A. ; Seiffert, S. Hybrid Microgels with Thermo-Tunable Elasticity for Controllable Cell Confinement. Advanced Healthcare Materials 2015, 4 1841-1848. Publisher's VersionAbstract

Stimuli‐responsive hydrogels are able to change their physical properties such as their elastic moduli in response to changes in their environment. If biocompatible polymers are used to prepare such materials and if living cells are encapsulated within these networks, their switchability allows the cell–matrix interactions to be investigated with unprecedented consistency. In this paper, thermo‐responsive macro‐ and microscopic hydrogels are presented based on azide‐functionalized copolymers of poly(N‐(2‐hydroxypropyl)‐methacrylamide) and poly(hydroxyethyl methacrylate) grafted with poly(N‐isopropylacrylamide) side chains. Crosslinking of these comb polymers is realized by bio‐orthogonal strain‐promoted azide–alkyne cycloaddition with cyclooctyne‐functionalized poly(ethylene glycol). The resulting hybrid hydrogels exhibit thermo‐tunable elasticity tailored by the polymer chain length and grafting density. This bio‐orthogonal polymer crosslinking strategy is combined with droplet‐based microfluidics to encapsulate living cells into stimuli‐responsive microgels, proving them to be a suitable platform for future systematic stem‐cell research.

2015_advhealthcaremater_hackelbusch.pdf
Gaudreault, R. ; Di Cesare, N. ; van de Ven, T. G. M. ; Weitz, D. A. Structure and Strength of Flocs of Precipitated Calcium Carbonate Induced by Various Polymers Used in Papermaking. Industrial & Engineering Chemistry Research 2015, 54, 6234-6246. Publisher's VersionAbstract

Because of persistent economic pressure on cost reduction, inorganic fillers such as precipitated calcium carbonate (PCC) have become increasingly economically attractive in the papermaking process. The increase of filler level in paper can be achieved by adding it to pulp prior to the headbox, either as individual filler particles or as preaggregates, while maintaining paper strength and minimizing their negative impact. Consequently, the floc structure and strength of PCC aggregates was studied using flocculants and dry strength agents, using static light scattering/diffraction (SLS), real time fluorescent video imaging (RTFVI), image analysis, photometric dispersion analysis (PDA), and scanning electron microscopy (SEM). It was found that PEO/cofactor induced PCC aggregates were weaker at high shear and far more irreversible than those induced by the partially hydrolyzed polyvinyl formamide copolymerized with acrylic acid (PVFA/NaAA) or cationic starch. Flocs produced at low polymer dosages were smaller and weaker than those produced at higher dosages. The number of discrete PCC particles in aggregates was measured using real time fluorescent video imaging combined with image analysis. Finally, we speculate that when two scalenohedral crystal type PCC particles aggregate, there is a small effective surface area to bind them, mainly through classical bridging or charge neutralization flocculation. Moreover, additional polymer adsorption results in higher coverage of the external and internal surfaces and prevents further aggregation due to electrosteric repulsion.

2015_iec_caudreault.pdf
Klein, A.  M. ; Mazutis, L. ; Akartuna, I. ; Tallapragada, N. ; Veres, A. ; Li, V. ; Peshkin, L. ; Weitz, D.  A. ; Kirschner, M.  W. Droplet Barcoding for Single-Cell Transcriptomics Applied to Embryonic Stem Cells. Cell 2015, 161, 1187 - 1201. Publisher's VersionAbstract

It has long been the dream of biologists to map gene expression at the single-cell level. With such data one might track heterogeneous cell sub-populations, and infer regulatory relationships between genes and pathways. Recently, RNA sequencing has achieved single-cell resolution. What is limiting is an effective way to routinely isolate and process large numbers of individual cells for quantitative in-depth sequencing. We have developed a high-throughput droplet-microfluidic approach for barcoding the RNA from thousands of individual cells for subsequent analysis by next-generation sequencing. The method shows a surprisingly low noise profile and is readily adaptable to other sequencing-based assays. We analyzed mouse embryonic stem cells, revealing in detail the population structure and the heterogeneous onset of differentiation after leukemia inhibitory factor (LIF) withdrawal. The reproducibility of these high-throughput single-cell data allowed us to deconstruct cell populations and infer gene expression relationships.

2015_cell_klein.pdf
Macosko, E.  Z. ; Basu, A. ; Satija, R. ; Nemesh, J. ; Shekhar, K. ; Goldman, M. ; Tirosh, I. ; Bialas, A.  R. ; Kamitaki, N. ; Martersteck, E.  M. ; et al. Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets. Cell 2015, 161, 1202 - 1214. Publisher's VersionAbstract

Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq, a strategy for quickly profiling thousands of individual cells by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell’s RNAs, and sequencing them all together. Drop-seq analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts’ cell of origin. We analyzed transcriptomes from 44,808 mouse retinal cells and identified 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes. Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution.

2015_cell_macosko.pdf
Zhou, Y. ; Park, J. ; Shi, J. ; Chhowalla, M. ; Park, H. ; Weitz, D. A. ; Ramanathan, S. Control of Emergent Properties at a Correlated Oxide Interface with Graphene. Nano Letters 2015, 15, 1627-1634. Publisher's VersionAbstract

Electrolyte gating of complex oxides enables investigation of electronic phase boundaries and collective response to strong electric fields. The origin of large conductance modulations and associated emergent properties in such field effect structures is a matter of intense study due to competing contributions from electrostatic (charge accumulation) and electrochemical (crystal chemistry changes) effects. Vanadium dioxide (VO2) is a prototypical correlated insulator that shows an insulator-to-metal transition at ∼67 °C and recent studies have noted a vast range of electronic effects in electric double-layer transistors (EDLT). In this study, we demonstrate that the response of electrolyte gated VO2 devices can be deterministically controlled by inserting a monolayer of graphene at the oxide–electrolyte interface. Several electrolytes as well as dopants (such as lithium ions and protons) were employed in EDL transistors to show that graphene serves as an inert barrier that successfully protects the oxide surface from chemical reactions. This monolayer interface has a striking effect on resistance modulation in the vanadium dioxide transistor channel up to several orders of magnitude and enables retention of the insulating phase. The studies allow new insights into the response of correlated insulators in EDLTs and inform design of correlated oxide–2D heterostructures for electronics and sensors.

2015_nanoletter_zhou.pdf
Russell, E. R. ; Spaepen, F. ; Weitz, D. A. Anisotropic elasticity of experimental colloidal Wigner crystals. Phys. Rev. E 2015, 91, 032310. Publisher's VersionAbstract
Colloidal particles interacting via a long-range repulsion can, in contrast to hard-sphere systems, exhibit crystalline ordering at low volume fraction. Here we experimentally investigate the structure and properties of such “colloidal Wigner crystals.” We find a body-centered-cubic crystalline phase at volume fractions of ϕ≳15%, which exhibits large fluctuations of individual particles from their average positions. We determine the three independent crystalline elastic constants and find that these crystals are very compliant and highly anisotropic.
2015_pre_russell.pdf
Bannwarth, M. B. ; Utech, S. ; Ebert, S. ; Weitz, D. A. ; Crespy, D. ; Landfester, K. Colloidal Polymers with Controlled Sequence and Branching Constructed from Magnetic Field Assembled Nanoparticles. ACS Nano 2015, 9 2720-2728. Publisher's VersionAbstract

The assembly of nanoparticles into polymer-like architectures is challenging and usually requires highly defined colloidal building blocks. Here, we show that the broad size-distribution of a simple dispersion of magnetic nanocolloids can be exploited to obtain various polymer-like architectures. The particles are assembled under an external magnetic field and permanently linked by thermal sintering. The remarkable variety of polymer–analogue architectures that arises from this simple process ranges from statistical and block copolymer-like sequencing to branched chains and networks. This library of architectures can be realized by controlling the sequencing of the particles and the junction points via a size-dependent self-assembly of the single building blocks.

2015_acsnano_bannwarth.pdf
Kanai, T. ; Boon, N. ; Lu, P. J. ; Sloutskin, E. ; Schofield, A. B. ; Smallenburg, F. ; van Roij, R. ; Dijkstra, M. ; Weitz, D. A. Crystallization and reentrant melting of charged colloids in nonpolar solvents. Phys. Rev. E 2015, 91, 030301. Publisher's VersionAbstract

We explore the crystallization of charged colloidal particles in a nonpolar solvent mixture. We simultaneously charge the particles and add counterions to the solution with aerosol-OT (AOT) reverse micelles. At low AOT concentrations, the charged particles crystallize into body-centered-cubic (bcc) or face-centered-cubic (fcc) Wigner crystals; at high AOT concentrations, the increased screening drives a thus far unobserved reentrant melting transition. We observe an unexpected scaling of the data with particle size, and account for all behavior with a model that quantitatively predicts both the reentrant melting and the data collapse.

2015_pre_kanai.pdf
Lee, W. C. ; Kim, K. ; Park, J. ; Koo, J. ; Jeong, H. Y. ; Lee, H. ; Weitz, D. A. ; Zettl, A. ; Takeuchi, S. Graphene-templated directional growth of an inorganic nanowire. Nature Nanotechnology 2015, 10, 423-428. Publisher's VersionAbstract

Assembling inorganic nanomaterials on graphene is of interest in the development of nanodevices and nanocomposite materials, and the ability to align such inorganic nanomaterials on the graphene surface is expected to lead to improved functionalities, as has previously been demonstrated with organic nanomaterials epitaxially aligned on graphitic surfaces. However, because graphene is chemically inert, it is difficult to precisely assemble inorganic nanomaterials on pristine graphene. Previous techniques based on dangling bonds of damaged graphene, intermediate seed materials and vapour-phase deposition at high temperature have only formed randomly oriented or poorly aligned inorganic nanostructures. Here, we show that inorganic nanowires of gold(I) cyanide can grow directly on pristine graphene, aligning themselves with the zigzag lattice directions of the graphene. The nanowires are synthesized through a self-organized growth process in aqueous solution at room temperature, which indicates that the inorganic material spontaneously binds to the pristine graphene surface. First-principles calculations suggest that this assembly originates from lattice matching and π interaction to gold atoms. Using the synthesized nanowires as templates, we also fabricate nanostructures with controlled crystal orientations such as graphene nanoribbons with zigzag-edged directions.

lee2015.pdf
Fischer, A. E. ; Wu, S. K. ; Proescher, J. B. G. ; Rotem, A. ; Chang, C. B. ; Zhang, H. ; Tao, Y. ; Mehoke, T. S. ; Thielen, P. M. ; Kolawole, A. O. ; et al. A high-throughput drop microfluidic system for virus culture and analysis. Journal of Virological Methods 2015, 213, 111-117. Publisher's VersionAbstract

High mutation rates and short replication times lead to rapid evolution in RNA viruses. New tools for high-throughput culture and analysis of viral phenotypes will enable more effective studies of viral evolutionary processes. A water-in-oil drop microfluidic system to study virus–cell interactions at the single event level on a massively parallel scale is described here. Murine norovirus (MNV-1) particles were co-encapsulated with individual RAW 264.7 cells in 65 pL aqueous drops formed by flow focusing in 50 μm microchannels. At low multiplicity of infection (MOI), viral titers increased greatly, reaching a maximum 18 h post-encapsulation. This system was employed to evaluate MNV-1 escape from a neutralizing monoclonal antibody (clone A6.2). Further, the system was validated as a means for testing escape from antibody neutralization using a series of viral point mutants. Finally, the replicative capacity of single viral particles in drops under antibody stress was tested. Under standard conditions, many RNA virus stocks harbor minority populations of genotypic and phenotypic variants, resulting in quasispecies. These data show that when single cells are encapsulated with single viral particles under antibody stress without competition from other virions, the number of resulting infectious particles is nearly equivalent to the number of viral genomes present. These findings suggest that lower fitness virions can infect cells successfully and replicate, indicating that the microfluidics system may serve as an effective tool for isolating mutants that escape evolutionary stressors.

fischer2015.pdf
Köster, S. ; Weitz, D. A. ; Goldman, R. D. ; Aebi, U. ; Herrmann, H. Intermediate filament mechanics in vitro and in the cell: from coiled coils to filaments, fibers and networks. Current Opinion in Cell Biology 2015, 32, 82-91. Publisher's VersionAbstract

Intermediate filament proteins form filaments, fibers and networks both in the cytoplasm and the nucleus of metazoan cells. Their general structural building plan accommodates highly varying amino acid sequences to yield extended dimeric α-helical coiled coils of highly conserved design. These ‘rod’ particles are the basic building blocks of intrinsically flexible, filamentous structures that are able to resist high mechanical stresses, that is, bending and stretching to a considerable degree, both in vitro and in the cell. Biophysical and computer modeling studies are beginning to unfold detailed structural and mechanical insights into these major supramolecular assemblies of cell architecture, not only in the ‘test tube’ but also in the cellular and tissue context.

koster2015.pdf
Jensen, M. H. ; Morris, E. J. ; Goldman, R. D. ; Weitz, D. A. Emergent properties of composite semiflexible biopolymer networks. BioArchitecture 2015, 4 138-143. Publisher's VersionAbstract

The semiflexible polymers filamentous actin (F-actin) and intermediate filaments (IF) both form complex networks within the cell, and together are key determinants of cellular stiffness. While the mechanics of F-actin networks together with stiff microtubules have been characterized, the interplay between F-actin and IF networks is largely unknown, necessitating the study of composite networks using mixtures of semiflexible biopolymers. We employ bulk rheology in a simplified in vitro system to uncover the fundamental mechanical interactions between networks of the 2 semiflexible polymers, F-actin and vimentin IF. Surprisingly, co-polymerization of actin and vimentin can produce composite networks either stronger or weaker than pure F-actin networks. We show that this effect occurs through steric constraints imposed by IF on F-actin during network formation and filament crosslinking, highlighting novel emergent behavior in composite semiflexible networks.

jensen2015.pdf

[*Equal contribution]

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