Well, maybe that is overstating it. However, PLPs, as we call them, are pretty cool. This massive collaborative effort between Ashley Brown, Sarah Stabenfeldt, Tom Barker, Wilbur Lam, Nina Guzzetta, Alexander Alexeev, and yours truly was recently published online in Nature Materials. I won’t rehash the whole paper here – you should go read it for yourself. I will point out, however, that working on this stuff has been the most fun I have ever had in science. The team that Tom Barker, Ashley Brown, and I assembled in our goal to replicate key aspects of platelet behavior has been a blast to work with, and I sincerely hope that we can continue to push forward on what I think is an exciting intersection between biology, mechanical engineering, hematology, and polymer chemistry & physics.
Updates have been challenging with all of the cross-country move activities. However, I finally found a few minutes to at least post on the newest papers from the group. First comes a collaboration with the Fernandez-Nieves group and Urs Gasser at PSI that we published in JCP entitled “Form factor of pNIPAM microgels in overpacked states“. Actually, those two groups did most (all?) of the heavy lifting there, performing some very nice neutron scattering studies on mixed phases of pNIPAm and deuterated-pNIPAm microgels. However, I don’t mean to diminish the importance of all the dirty work Emily did on the synthesis side, preparing low polydispersity samples of both types of microgels in the same size range – not an easy task, to be sure. The take home message from the work is that microgels don’t start deswelling until they are actually touching – that is there is no “osmotic deswelling” effect in packed phases and the particles maintain their dilute solution hydrodynamic sizes until they start getting mechanically squeezed for space.
The second new paper (published in Langmuir) comes from former group member Dr. Ling Zhang and current grad student Mark Spears entitled “Tunable Swelling and Rolling of Microgel Membranes“. Here they have shown that when microgel-based multilayers are prepared under specific conditions, a pH-induced swelling event can cause the film to delaminate as a single, continuous sheet (see figure). When bilayer films composed of two different types of microgels (even just different size microgels) are prepared, the delamination event is accompanied by differential swelling, which drives rolling into a tube or scroll. The rolled films are cool looking, but we also think this work tells us a great deal about the fundamental interactions and swelling properties of microgel thin films.
Shalini and Caroline recently collaborated to write an Accounts of Chemical Research article on “Microgel Mechanics in Biomaterial Design“. The work is a review of some of our efforts in at the microgel/bio interface, with the highlights being depicted in the artwork to the right (drawn by Prof. Lyon in ArtStudio on an iPad). In the leftmost depiction, we see that polyelectrolyte/microgel assemblies, when formed into a thin film, can mediate cell attachment and spreading in a manner that appears to relate to the viscoelasticity of the film, as opposed to being related to just the elasticity. We have also demonstrated that ultrasoft microgels can deform to a large degree when faced with transport through small pores (center image). This may be relevant for renal clearance of injectable drug delivery vehicles. Finally, on the right we see a cartoon representation of a core/shell microgel with a shell that can gate or tune the release of the interior microgel contents. Please feel free to share any thoughts on the article, which is just a small preamble to all the nano/micro/bio stuff churning in the group right now – stay tuned for some very cool stuff that should be coming out in the near future!
Following up on the last post (December? Wow – sorry for the radio silence – things have been busy), I wanted to bring the special issue of Soft Matter on “Reconfigurable Soft Matter” to everyone’s attention. This issue was masterfully edited by Anna Balazs and Joanna Aizenberg to contain a rich array of approaches to soft materials. One thing I find wonderful about the issue is the span from the macroscopic (see: Bioinspired self-shaping materials) to the microscopic (see: Microstructured membranes) to the molecular (see: UV-burstable microcapsules based on azobenzene). Similarly, the issue spans what might be called “engineering approaches” to ones focused more on the fundamental physical sciences of such structures. If you have interest in the field, I encourage you to take a look – the issue should serve for some time as a nice entry point into the field for newcomers, and as a “2014 status report” for those already embedded in the field.
I guess I should have just waited a few days to include this in the last post. Anyway, the manuscript “Microgel Film Dynamics Modulate Cell Adhesion Behavior” was published on line this week in the journal Soft Matter. This is another collaboration between my group and the Garcia group, with Shalini, Mark, Jeff, and Hiro taking the lead on these studies. In this paper, we describe how the “self-healing” properties of microgel-based multilayer thin films appear to modulate cell attachment and spreading. The hypothesis is that the viscous behavior (as opposed to the elasticity) of the film is responsible for cells failing to adhere and spread on reconfigurable interfaces. This comes about through balancing the energy required to remodel the interface with the force exerted by cells when forming focal adhesions. In principle, this is is a relevant phenomenon for tissue engineering, since the film viscosity is related to the timescale of cell spreading and proliferation and could therefore be used to further control cell phenotype and tissue remodeling.
In the last few weeks we have seen three new papers show up online. First, we have “Host response to microgel coatings on neural electrodes implanted in the brain” published in Journal of Biomedical Materials Research Part A. Stacy Gutowski from the Garcia group did all the heavy lifting here, wherein she implanted neural electrodes in live rodents and subsequently analyzed the wound healing response to electrodes with and without microgel-based coatings. The coatings were made and analyzed largely by two former Lyon group members: Toni South and Jeff Gaulding. The take home message here is that the coatings did not result in dramatically improved wound healing – a disappointing result, but it is gratifying to see our materials used in such a complex biomedical application.
More recently, Kim Clarke published a paper entitled “Modulation of the Deswelling Temperature of Thermoresponsive Microgel Films” in Langmuir. Kim has demonstrated that simple copolymerization approaches can be used to tightly control microgel deswelling temperatures, and that constructing films of those particles permits tuning of film thermal responses. Importantly, films composed of mixed populations of different microgels result in composite thermal responses suggesting that individual microgels retain their individual deswelling properties and are not greatly influenced by the overall film structure. For example, mixing two microgels with distinct responses in a single film will produce two distinct deswelling transitions in the film. Kim is continuing this work to further understand the role of microgel structure and polyelectrolyte interactions in film volume phase transitions.
Finally, Langmuir Invited Feature Article entitled “Dynamic Materials from Microgel Multilayers” just showed up online. Mark, Emily, and Jeff worked together to summarize the group’s efforts over the last few years on self-healing and reconfigurable interfaces composed of microgel/polyelectrolyte complexes. With work continuing on this subject, we hope that this is just the tip of the iceberg in terms of our advances in self-healing materials.
A new themed issue of Polymer Chemistry came out today, including an article from the group that I have already written about. Note that we also got a little artwork on the back cover, thanks to artist Jesse Larson. Check it out – the issue is well edited and covers a broad range of approaches to self-healing materials, with a focus (of course) on polymer chemistry. Enjoy…
Just a quick post to note that a new review article from the group, “Colloid-matrix assemblies in regenerative medicine”, appeared online today in Current Opinion in Colloid and Interface Science. The paper is essentially a short discussion of the extracellular matrix, its properties, and how one might recapitulate its function by using colloidal particles as modifiers. The vision for this and the writing efforts were split between Kim Clarke from our group, and Alison Douglas from the Barker lab, with Dr. Ashley Brown offering additional insight and ideas in the paper’s construction. Check it out – any comments/thoughts on the subject are certainly welcome.
A new paper from the group came out today in ACS Macro Letters entitled “Packed Colloidal Phases Mediate the Synthesis of Raspberry-Structured Microgel Heteroaggregates“. The paper basically describes how you can take advantage of the “self-healing” properties of packed microgel assemblies to decorate other colloidal particles with microgels. Basically, a “hard” particle like a poly(styrene) or silica sphere can be dispersed into a viscous microgel fluid, or a packed glassy phase, and then the microgels that are in intimate contact with that “defect” can be coupled to its surface. The resultant raspberry structured particles then have the hybrid properties of a dense core and a hydrophilic hydrogel shell. Whereas similar structures have bee made by other approaches, we find this method very scalable and easy to use. The approach allows for a variety of different materials to be made without worrying about the somewhat finicky colloid chemistry associated with heteroaggregation from dilute media, which is another approach to making such materials.
Jeff and Shalini led this work and a former REU student, Danielle Montanari (currently at Utah) helped tremendously during her time here. These particles are now being used in a collaboration with the McDevitt lab – we hope to tell you about that work soon – stay tuned.
This is just a quick post describing some new work that is now available online. First up, we have Development of Self-Assembling Mixed Protein Micelles with Temperature-Modulated Avidities that is online at Advanced Healthcare Materials. This is another collaborative effort between my group and Tom Barker’s, with his former student Allyson Soon being the lead author. In this work, Allyson developed block copolymer micelles composed of elastin-like polypeptides with fibrinogen-binding peptides (GPRP) tethered to the outer micelle surface. By switching the micelle structure (and hence the GPRP binding availability) she was able to thermally switch micelle-fibrinogen binding. We supported this very nice work with some light scattering studies (Mike Smith) and some AFM (Emily Herman). Allyson is currently a postdoc at UCLA with Tatiana Segura and seems to be doing quite well. Since I am also at UCLA right now on sabbatical, and have been infiltrating the Segura group meetings, Allyson has unfortunately not rid herself of me yet – I am still bugging her…
The second new paper is Plastic Deformation, Wrinkling, and Recovery in Microgel Multilayers, which is online at Polymer Chemistry (RSC). Jeff Gaulding and Mark Spears teamed up on this work, which was invited as part of a special issue on Self-Healing Polymers. This is an extension of our previous work on microgel-based, LbL-fabricated, thin films that can be damaged by deformation, but then re-heal upon immersion in water. Perhaps the two key results from this work involved the use of AFM to image the films during deformation and damage, and the use of humid environments to induce slow healing. The AFM studies conclusively show that the damage induced during linear stress is plastic deformation or stretching of the film, with wrinkling occurring after release of the stress. Before these studies, it was not at all clear whether the damage patterns observed were wrinkles or cracks, making determination of the damage and healing pathways difficult. Secondly, we did not have a clear sense of what drove healing. Whereas hydration was important, it was not known whether surface tension or film swelling was driving healing. By precisely controlling the humidity around the film, we were able to show that film swelling is sufficient to induce healing, suggesting that the polymer mobility in the film during swelling is sufficient to restore the film to a state approximating the as-prepared structure.
If you have the time and interest, go check out both papers, and feel free to provide any feedback you feel is warranted.
A new issue of Colloid and Polymer Science (volume 291, issue 1) hit the newsstands this week, and this issue is noteworthy for its focus on Functional Polymeric Microspheres. The issue was guest-edited by Haruma Kawaguchi and Masayoshi Okubo, and they did a great job of getting people from a wide span of areas to contribute. I will also note that our group contributed, with Jeff and group alumnus Toni co-authoring “Hydrolytically degradable shells on thermoresponsive microgels”. In this paper, we describe how core swelling restriction/compression can be modulated by controlled degradation of cross-links in the polymer shell. A variety of tools were employed to better understand these particles, including dynamic light scattering, asymmetrical flow field-flow fractionation–multiangle light scattering, and atomic force microscopy. Congrats to Jeff and Toni for some very nice work. Happy reading…
The latest Accounts of Chemical Research is a special issue on Gene Silencing and Delivery. We were fortunate to have been invited to contribute to the volume, while also having the issue adorned with cover art developed by our very own Mike Smith.
Click the image for a higher resolution version. We should also thank Hiro for alerting us to the program used to create the artwork, Shade. There is a bit of a steep learning curve on it, but they tell me it is fantastic once you get going. Anyway, enjoy the issue – there are some tremendous contributions spanning a huge range of research – definitely a must-read.
A couple of new papers from the group have appeared online. Jeff has written up his very nice work on disulfide containing microgels – the manuscript recently appeared online in Macromolecules. In this paper, we demonstrate the ability to synthesize redox-sensitive microgels using a low temperature synthesis approach originally developed in the group by Xiaobo Hu. The erosion properties of these particles were studied in collaboration with Mike using A4F/MALS. Additionallly, John Hyatt from Alberto Fernandez-Nieves’ group in the School of Physics helped out with rheology studies of disulfide based inter-microgel cross-linking. Together, the results illustrate our ability make well-defined microgels with controllable porosities and erosion properties using disulfide-based cross-linkers. We are currently employing these strategies in some controlled-release applications.
In the second paper, Mike has written up an Accounts of Chemical Research article on siRNA delivery. This manuscript mainly highlights our work with the McDonald group in the School of Biology in which we use peptide-based targeting strategies to deliver siRNA to ovarian cancer cells. Additionally, the manuscript describes our “synthetic toolbox” for the construction of complex core/shell microgel architectures, which we have been developing for the last 13 years. Our hope is to translate this toolbox into the development of truly functional vehicles…stay tuned.
A new paper from the group just appeared in Macromolecules ASAP. “Tunable Encapsulation of Proteins within Charged Microgels” describes some light scattering studies by Mike Smith wherein he used the Calypso coupled to MALS and dRI detection to study the loading of cytochrome C within pNIPAm-AAc microgels. The take-home message here is that for the case of cationic protein encapsulation within anionic microgels, the increase in capacity is not a simple linear function of anion density. For example, a ~10-fold increase in protein loading is obtained by increasing the AAc content from 20 mol% to 30 mol%. Additionally, the loading is extremely sensitive to ionic strength, with very tight protein binding being observed at ~20 mM salt. Nearly quantitative release is then obtained upon raising the ionic strength to physiological levels (~140 mM), suggesting a mechanism for triggering the release in vivo. We hope to use the analytical methods presented in this paper to perform detailed, quantitative studies of protein-microgel affinity for a variety of proteins that are of interest in pharma applications.
A new paper from the group is out today that has arisen out of our collaboration with Henry White at U. of Utah and his student Deric Holden. The basic idea is this: Grant Hendrickson from our group previously observed, using a simple filtration set-up, that microgels could pass through pores that were nearly 10-times smaller than the equilibrium diameter of the spheres. Continue reading “A tight sqeeze”