platelet-like particles will cure what ails you

Well, maybe that is overstating it.  However, PLPs, as we call them, are pretty cool.  This massive collaborative effort between Ashley BrownSarah Stabenfeldt, Tom Barker, Wilbur LamNina 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.  

catching up

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.

la-2014-00860t_0007The 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.

Happy reading!

new Accounts article

ar-2014-00131v_0011Shalini 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!


reconfigurable materials

GAFollowing 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.

another new paper

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.

a few new papers

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.

new issue of polymer chemistry

wrinklesA 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…

pathological science

I was recently re-reading the transcript of Irving Langmuir‘s classic Pathological Science lecture from 1953 (download the PDF) and thought I might drop a post on here about it.  For most physical scientists, I imagine that the talk is well known.  There are extensive websites on the subject, as well as the obligatory Wikipedia page, so there is no need to rehash all of that here.  However, it did strike me that maybe a restating of the lecture’s main points would be of some use, since the talk is apparently not as well known amongst many of my colleagues in the biosciences.  So, Langmuir defined pathological science as having the following properties (Langmuir’s words in quotes): Continue reading “pathological science”

some thoughts on the ECM

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.

makin’ raspberries

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.

designer blood clots

Just thought I would put up a short post linking to a new press release on our work.  Tom Barker’s group has taken the lead on our rapidly growing hemostasis/artificial platelet project, and he spent the day today presenting and talking to the press about the work at the AAAS meeting. While Tom’s group has brought their deep understanding of ECM biology and engineering to the project, we have contributed new microgels that utilize molecular evolution work out of Tom’s lab to create artificial platelets. The ability of these artificial platelets to speed up clotting has been investigated in endothelialized microfluidic devices developed by Wilbur Lam’s group, making for a very exciting and dynamic collaboration. Driving this project forward, from the polymer synthesis to the ongoing (and very promising) animal studies, has been Dr. Ashley Brown, who is working with new Lyon Group grad students Caroline and Kenny, along with undergrad extraordinaire Kabir. Stay tuned – hopefully more of the great stuff going on in this project will be revealed soon.

new issue of Colloid and Polymer Science

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…

cancer – prevention vs. treatment

I thought I would share an interesting presentation by Craig Thompson, President and CEO of the Memorial Sloan Kettering Cancer Center.  If you have 30 minutes to spare, it is worth a look. For some time now, we have known that tumors have a much higher glucose demand than healthy tissues. However, this fact rarely translates into dietary advice. The hypothesis is that if tumor needs glucose, then consuming a diet that is low in carbohydrate will effectively starve the tumor and result in necrosis. A diet that contains a higher proportion of calories from fat would in principle be less oncogenic.  Thompson acknowledges in the Q&A that current dietary advice would argue against a high fat diet due to the focus on “heart-healthy” diets, but that we need to balance that against the desire to prevent cancer – waiting to treat the disease is clearly not good enough. It is unfortunate that he doesn’t discuss the fact that the demonization of cholesterol and fat is probably misguided. Nonetheless, there are also some interesting ideas out there on using a low carbohydrate dietary strategy to treat advanced cancer, including the work of Eugene Fine and Richard Feinman. You can download a recent paper on the subject here, in which a small (10 patient) sample was studied.  You can read Eugene’s discussion of the work on Richard’s blog – it is encouraging to note that even in this very small study, there was a statistically meaningful correlation between disease stabilization (with one case of remission) and dietary ketosis.  Getting back to the original point of this post, have a look at Thompson’s presentation (below).  Hopefully in the future we can move in a the direction of funding for dietary cancer prevention – there is good reason to believe in this “tumor starvation” approach.  Continue reading “cancer – prevention vs. treatment”

a future in graphic design?

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.

the importance of being self-critical

In laboratory science-based fields, we are accustomed to performing research using the principles of the scientific method. To summarize, we form a hypothesis, conduct an experiment, collect data, analyze and interpret the data, and then draw conclusions that may or may not be aligned with the initial hypothesis. We then cycle back with a revised hypothesis and repeat the method. For this process to work, the experiments being performed must be designed to limit the number of possible conclusions, hence the need for appropriate controls. Finally, we try to use Occam’s Razor when drawing conclusions; the simplest, most assumption-free interpretation of the data should be explored first, before moving on to more complex explanations.

Recently I have been reading literature from various disciplines associated with obesity and heart disease, and the relationship between diet and those maladies. To be blunt, I have been amazed at what folks can get away with in the supposedly peer-reviewed literature. In my opinion, coming at it as an experimentalist, some of what I present below crosses the line from being poorly done to just plain irresponsible. For the sake of brevity, I will present these examples by linking to writers who have already gone through the process of dissecting the primary literature. I don’t think it is necessary for me to re-do analyses that have already been ably done. However, I want to make it clear that some of these writers have economic interest in the whole argument – they are selling books, are on lecture circuits, etc. By linking to those articles, I am not endorsing their products – I do however find some of what they have to say quite useful.

Continue reading “the importance of being self-critical”