Morgan Stanton – Soft Matter Blog

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Jamming and unjamming of cell co-cultures

27 Sep 2016

Cell behavior is highly dependent on its surrounding environment, including neighboring and adjacent cells. Individual cells can merge and form a solid-like state for a “jamming” effect or a highly dense cell mass can disperse and become more mobile, for an “unjamming” transition. Both behaviors have been observed in complex, multi-cellular interactions such as wound healing, embryonic development, and tumor metastasis.

To investigate jamming-unjamming cell transitions, researchers from Brown University describe methods to quantify cell-cell interactions in a recently published Soft Matter article. The group observed co-cultures of epithelial cells and mesenchymal cells and their ability to cluster (jamming) or remain mobile and unconnected (unjamming). Epithelial cells collectively organize to form dense multi-layered cell sheets while mesenchymal cells avoid cell-cell bonds and are capable of individual migration.

Cell clustering ability with different ratios of epithelial (red) and mesenchymal cells (green)

By increasing the number of mesenchymal cells in an epithelial cell population, the research group observed a reduction in epithelial cell clustering causing a significant disruption in cell sheet formation and confluency. The addition of mesenchymal cells also increased the average collective cell velocity and decreased cell proliferation, reducing the typical jamming behavior of epithelial cells.

The research provides important biophysical data for collective cell behavior as well as introducing new parameters to control cell jamming-unjamming transitions.

Interested in this research? Read the full article for free until 31/10/2016 using a registered RSC account:
Clustering and jamming in epithelial-mesenchymal co-cultures
Marielena Gamboa Castro, Susan E. Leggett, and Ian Y. Wong
Soft Matter, 2016, Advance Article
DOI: 10.1039/C6SM01287F

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About the webwriter

Dr. Morgan M. Stanton is currently a postdoctoral researcher at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany. Her research focuses on the cell-material interface material and properties regulating cell behavior.

Read more about Morgan’s research publications and follow her on Twitter: @morg368.

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Elastic Properties of the Brain

21 Jul 2016

Young's modulus of the pituitary gland measured with AFM

Large variations in stiffness of the pituitary gland

The composition of the human body varies widely in rigidity from soft organs and fat to stiff bones. The rigidity and stiffness of the body plays vital roles in cell behavior and tumor development, so measuring and understanding tissue stiffness is important for the design of biomaterials and cancer treatment.

In a recent Soft Matter article, a multidisciplinary group from Grenoble, France, has probed the elastic modulus of the brain, specifically the pituitary gland, which produces and regulates hormones. Unlike previous attempts, which have observed tissues at the macro scale (mm, cm), the research team has investigated the brain at the micron level.

At this subcellular scale, it was revealed that the tissue was not uniform in elasticity and there were vast differences in stiffness throughout the gland. Using atomic force microscopy (AFM), rigidity measurements from 1 kPa to 50 kPa were recorded with localized islands of increased stiffness observed.

This has been the first attempt to measure elasticity of the pituitary gland at the micron scale, providing research that could help understand cellular organization and the mechanism of tumor growth in the brain.

Interested in this research? Read the full article for free until 03/07/2016 using a registered RSC account:

AFM mapping of the elastic properties of brain tissue reveals kPa μm^-1 gradients of rigidity
Nicolas Bouchonville, Mikaël Meyer, Christophe Gaude, Emmanuel Gay, David Ratel, and Alice Nicolas
Soft Matter, 2016,12, 6232-6239
DOI: 10.1039/C6SM00582A

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About the webwriter

Read more about Morgan’s research publications and follow her on Twitter: @morg368.

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Complex polymer nanostructures with solvent annealing

24 Feb 2016

Fabrication of nanopatterns or nanostructures at a surface is often limited to the accuracy and resolution of the instrument. Photolithography is successful at producing nanostructures, but the properties are restricted to the dimensions of the chosen mask. In a current Soft Matter article, a collaborative research group has added an additional step to traditional photolithography to produce more complex micro- and nanostructures. Initially, nano ‘pre-patterns’ were formed on substrates with photolithography; cross-linked polystyrene (PS), poly(methyl methacrylate) (PMMA), or a hydroxyl terminated polymer (PS-PMMA-OH) were patterned as nanostripes on a silicon wafer surface. After the patterns were deposited, a second layer of block copolymer, PS-b-PMMA, was spincoated over the entire pre-pattern. Finally, samples were incubated in a sealed container with an open vial of acetone to anneal the layer of PS-b-PMMA. The solvent annealing of the block copolymer produced ordered nanostructures of PS-b-PMMA on top of the premade photolithography pattern. PS-b-PMMA structures and dimensions varied with annealing time but remained ordered due to the initial chemical pre-pattern. Unpatterned surfaces also developed nanostructure, but without any order to the polymer structures.

PS-b-PMMA nanopatterned polymer with acetone annealing

Nanopatterned polymer with solvent annealing

The mechanism of assembly of the block copolymer nanostructures was controlled by two factors: film thickness and migration of PMMA polymer chains from the bottom to the top of the surface as PMMA is more stable in an acetone vapor. The combination of solvent annealing and chemical pre-patterning perturbs the polymer chain configurational energy and interfacial energy to instigate the nanostructure formation. The polymer microdomains are formed while solvated and are retained after acetone removal. The control of nanopattern dimensions with chemical pre-patterning and solvent annealing expands the application range of traditional photolithography. This appealing fabrication procedure can be utilized by the seminconductor industry where complicated nanopatterns are used for data storage or electronics.

See the full Soft Matter article here:

Directed self-assembly of solvent-vapor-induced non-bulk block copolymer morphologies on nanopatterned substrates

Lei Wan, Shengxiang Ji, Chi-Chun Liu, Gordon S. W. Craig, and Paul F. Nealey

Dr. Morgan M. Stanton is currently a postdoctoral researcher at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany. She completed her Ph.D. in Chemistry from Worcester Polytechnic Institute in 2014. Read more about Morgan’s research publications here or you can follow her on Twitter @morg368.

Follow the latest Soft Matter publications and updates on Twitter @softmatter or on Facebook.

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Stable Liquid Drop Deformation with Nanoparticles

11 Jan 2016

Miniature reaction vessels, such as liquid marbles, have shown significant promise for millimeter scale and low volume chemical and biological experiments. Here, solid particles are trapped at the drop surface, separating the interior liquid from the surface, so the droplet does not stick to the substrate. For large scale applications, liquid marbles have some handicaps, including their lack of optical clarity and their restriction to only a spherical shape. In a recent full article in Soft Matter, a collaborative research team has recently discovered a liquid marble alternative, where nanoparticles are squeezed onto a drop surface to alter its shape while still maintaining optical transparency and reaction vessel properties.

Water drops and liquid plasticine deformed with nanoparticles

Deformed water drops and examples of liquid plasticine.

To create the stable deformation of a liquid, a single water drop is placed between two glass surfaces. The two glass surfaces were coated with layers of hydrophobic silica nanoparticles. When the drop was squeezed between the two modified glass layers and then released, nanoparticles detached from the glass and became adhered at the water droplet surface. Once the squeezing force was released and as the droplet tried to recover to its original spherical shape, the new nanoparticle layers on the drop surface became “jammed”, and permanently deformed the water droplet shape. The final shape of the deformed droplet was determined by the squeezing force, but the shape of the droplet could be adjusted by injecting new water into the drop, breaking apart the surface nanoparticles.

Moving from single water drops to larger volumes and exploiting the jamming properties of the nanoparticles, liquid plasticines could be developed. The water was deformed into a variety of shapes and used as small reaction vessels. Multiple plasticines were joined for controlled chemical reactions and then quickly separated using a hydrophobic knife. As proof of concept, a liquid plasticine with gold nanoparticles was connected to DC power (30 V) allowing the gold nanoparticles to migrate to the positive end of the plasticine. The liquid was then cut to separate the gold particles from the rest of the liquid. The permanently deformed drops and liquid plasticines offer new alternatives for liquid lenses and small volume liquid reactors.

See the full Soft Matter article here:

Liquid plasticine: controlled deformation and recovery of droplets with interfacial nanoparticle jamming

Xiaoguang Li, Yahui Xue, Pengyu Lv, Hao Lin, Feng Du, Yueyun Hu, Jun Shen, and Huiling Duan

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Modeling boron nitride nanopores for DNA sequence detection

12 Nov 2015

Quickly detecting DNA sequences with high accuracy is a significant goal for diagnostic medicine and genetics. The vast quantities of DNA and its small size make it difficult to achieve this goal. Nanopores offer a rapid method of detection by threading strands of DNA through a nanopore to detect individual nucleotides of the DNA. Solid-state nanopores separate two fluidic chambers and as the DNA passes through the pore, the pore becomes partially clogged and produces a blockage of ionic currents. The change in ionic current can be used to collect structural information from the DNA. Graphene has been well studied, experimentally and theoretically, for fabrication of these pores, but graphene produces significant complications with DNA detection. Graphene pores often contain material defects and DNA sticks to graphene, blocking the pores permanently, limiting detection capabilities. In a recent full article in Soft Matter, a collaborative research team tackles this issue by theoretically modeling DNA in a boron-nitride

Boron-nitride nanopore for double stranded DNA detection

Boron-nitride is composed of boron and nitride atoms in a honeycomb structure. The material is just as thin as graphene and exhibits similar desirable electrical and mechanical properties, but is more resistive to DNA adhesion, allowing the DNA to pass through the pore without permanent blockage. The research group used large-scale molecular dynamics to model double stranded DNA passing through boron-nitride pores ranging in size from 2.5 to 6.5 nm with an external voltage of 1.0 V. The smaller 2.5 nm pore size had greater blockage currents and a higher sensitivity to DNA threading through the pore than the larger pores due to its smaller cross-sectional area. Double stranded DNA composed of only adenine-thymine (A-T) or guanine-cytosine (G-C) nucleotide pairs were compared using the 2.5 nm pores with multiple applied voltages with the goal of understating the changes is current signal as the DNA passed through the pore. The greatest difference between A-T DNA and G-C DNA was observed at 1.0 V with G-C DNA exhibiting greater stretching and stress than the A-T DNA. Both sets of DNA passed readily through the boron-nitride nanopores without permanent blockage. In comparison, in modelling of DNA passing through graphene nanopores, DNA exhibited significant adhesion and breakage of the DNA at the pore. The large changes is current signal between A-T and G-C DNA and the lack of DNA adhesion using boron-nitride pores offer an exciting opportunity for future DNA sequencing. The molecular dynamic modeling presented will hopefully influence current experimental work in the development of DNA detection with nanopores.

See the full Soft Matter article here:

DNA translocation through single-layer boron nitride nanopores
Zonglin Gu, Yuanzhao Zhang, Binquan Luan and Ruhong Zhou
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Bacteria motors guided by liquid crystals

06 Oct 2015

Bacteria play a vital role in digestive, reproductive, and immune health within the human body. Recently, motile bacteria have been analyzed for their ability to transport cargo in confined environments. Bacteria convert surrounding chemical energy into mechanical work making them ideal for a micro scale motor. Although bacteria have proven capable of transporting cargo, directing where they swim and understanding how they interact with the cargo has been a challenge. A research group from University of Wisconsin-Madison, USA has utilized nematic liquid crystals to guide bacteria swimming and monitor how they associate with their cargo load. The full work is described in a recent communication article in Soft Matter.

A motile P. mirabilis cell pushes a non-motile C. albicans cell

The motile bacteria, P. mirabilis, were used to push non-motile fungal cells, C. albicans, in a directed path. Both the bacterial and fungal cells are found in patients with urinary tract infections. The urinary epithelium secretes layers of mucus within the urinary tract which is guided by external flow; molecules and cells in the urinary tract exhibit directional alignment due to the mucus flow. The proposed nematic liquid crystal environment with motile and non-motile cells represents a simple model of the human urinary tract. The alignment of the liquid crystal guides the bacteria and causes them to swim along the director field, similar to cells in the urinary epithelium. P. mirabilis were mixed with C. albicans and suspended within a 20 µm thick liquid crystal layer composed of disodium cromoglycate. Single P. mirabilis cells pushed the non-motile C. albicans cells along the director of the liquid crystal, to give straight or curved swimming tracks depending on the crystal orientation. The P. mirabilis were capable of reaching a velocity of 1 – 2 µm/s^-1 while transporting their fungal cell cargo.

For a greater understanding of the cargo transport mechanism, 2 µm diameter beads were mixed with the P. mirabilis. Bacteria transporting beads were capable of reaching velocities of 5 µm/s^-1. The hydrodynamics of the system of swimming bacteria and particles was analyzed with the mathematical model, regularized Stokeslets. The observed experimental swimming velocity correlated with numerical simulated results, with a clear trend of decreasing speed with increasing cargo size. The mathematical model suggests hydrodynamic interaction of the bacteria flagella and cargo load are an important for predicting system velocity. The work helps understand cellular interspecies interaction that is controlled with liquid crystal alignment.

See the full Soft Matter communication here:

Bacterial transport of colloids in liquid crystalline environments
Rishi R. Trivedi, Rina Maeda, Nicholas L. Abbott, Saverio E. Spagnolie, and Douglas B. Weibel
Soft Matter, Advanced Article, 2015
DOI: 10.1039/C5SM02041G

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Hydrogel capable of protein release using red light

10 Sep 2015

Hydrogel synthesis is a well-established method of incorporating cells, proteins, or drugs into a biocompatible polymer network. The majority of hydrogels are stimulated and cross-linked by a chemical reaction or UV light, but this can limit their use in vivo as these methods damage healthy cells. Using red light-stimulated hydrogels would be better suited for the therapeutic use of hydrogels, as it creates little photo damage to cells and red light can penetrate deeper into tissue than other light wavelengths. Such a hydrogel was developed by a research group at the Max Planck Institute for Polymer Research in Germany and is described in detail in a recently published full article in Soft Matter. The group describes a synthetic method of hydrogel formation using methoxy-modified azobenzene that activates the polymer complex under red light.

The hydrogel synthesis is based on the spontaneous formation of a supramolecular complex by combining an azobenzene (mAzo) derivative and β-cyclodextrin (β-CD). The two chemical species were individually grafted onto a poly(acrylic acid) (PAA) polymer backbone and mixed to form the red light-activated hydrogel. During exposure to red light, the azobenzene moiety in mAzo underwent isomerization from the trans to cis state, which was not hindered by the presence of β-CD. The process is reversible, with heat or blue light returning mAzo to the trans state. While the mAzo polymer remained in the trans state, the mAzo/β-CD complex maintained a gelatin formation, but once altered to the cis state by red light, the hydrogel destabilized and became a liquid. This sol-to-gel transition is explained by the high binding constant between trans mAzo and β-CD (K_a = 1546 M^-1) compared to low binding constant between cis mAzo and β-CD (K_a = 82.1 M^-1).

To demonstrate the hydrogel’s utility for medical applications, the hydrogel was loaded with the protein, bovine serum albumin (BSA). Exposure to red light dissolved the hydrogel and released ~83% of the protein into solution. If a piece of porcine tissue was placed between the red light source and the protein laden hydrogel, mAzo was still capable of transitioning to the cis state for disassembly of the gel and release of the BSA. The ability of the hydrogel to be activated through tissue using non-invasive and non-detrimental red light is an impressive step for the development of therapeutic and light-stimulated polymers for controlled drug or protein release.

See the full Soft Matter article here:

Supramolecular hydrogels constructed by red-light-responsive host–guest interactions for photo-controlled protein release in deep tissue
Dongsheng Wang, Manfred Wagner, Hans-Jürgen Butt, and Si Wu
Soft Matter, 2015, Advance Article
DOI: 10.1039/C5SM01888A

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A simple method for preventing nanoparticle-protein aggregation

25 Aug 2015

The interaction of proteins with nanoparticles has significant applications for clinical and biomedical therapies, specifically the field of theranostics, where diagnostic and therapeutic agents are combined into a single entity. Unfortunately, it has been well documented that attachment of proteins to nanoparticle surfaces leads to deformation of the protein and loss of protein activity. Aggregates of proteins form on the particle and induce aggregate formation of the particles themselves, hindering any theranostic capability.

In a recent communication in Soft Matter, researchers from Johns Hopkins University, USA, and Jawaharlal Nehru Centre for Advanced Scientific Research, India, describe a simple chemical method for solving this dilemma; addition of sugar. The naturally occurring disaccharide, trehalose, has demonstrated the ability to stabilize protein structures and shield them from thermal stress and dehydration. The protective nature of trehalose has been described by three hypotheses: (1) mechanical entrapment of the protein within the sugar molecules, (2) hydrogen bonding of the trehalose with the protein for chemical stabilization, (3) or water entrapment between the surface of the protein and trehalose. The research team exploited the protective properties of trehalose to insulate the protein, lysozyme, while the protein was exposed to silver nanoparticles, thus preventing denaturing of the protein.

Interaction of silver nanoparticles with lysozyme with varying trehalose concentrations

Without chemical stabilization, lysozyme aggregated on the nanoparticle surface and had significant structural deorganization. In the presence of trehalose, lysozyme maintained its active conformation and exhibited limited or no aggregation. By adjusting the concentration of trehalose in solution, nanoparticle-protein interactions were modulated. Analytical methods, including UV-vis absorbance, circular dichroism, and surface enhanced Raman spectroscopy (SERS) illustrated and characterized the changes is binding of the lysozyme to the silver nanoparticle surface and the enhanced stability of the protein. The proof-of-concept system created a biocompatible environment for nanoparticles and proteins to engage without compromising lysozyme structure or activity. The proposed method will facilitate the development of nanoparticle theranostics and opens new avenues for nanomedicine design.

See the full Soft Matter article here:

Revealing the trehalose mediated inhibition of protein aggregation through lysozyme-silver nanoparticle interaction
Soumik Siddhanta, Ishan Barman, and Chandrabhas Narayana
Soft Matter, 2015, Advance Article
DOI: 10.1039/C5SM01896J

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Soft Matter Blog

Author Archive

Jamming and unjamming of cell co-cultures

Elastic Properties of the Brain

Complex polymer nanostructures with solvent annealing

Stable Liquid Drop Deformation with Nanoparticles

Modeling boron nitride nanopores for DNA sequence detection

Bacteria motors guided by liquid crystals

Hydrogel capable of protein release using red light

A simple method for preventing nanoparticle-protein aggregation

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