Introducing a New Travel Award for the 2016 Annual Meeting: BPS Bridging Funds

In an effort to assist members in the current difficult funding situation, the Membership Committee will now be accepting applications for the Bridging Funds Travel Grant.

_D614733BPS understands that while some resources are limited, networking and staying up-to-date with current research is important to our members. This grant is designed to provide support to regular members who would normally attend the Annual Meeting, but cannot due to a temporary lack of funding. We encourage independent and principal investigators to apply for this travel grant to help alleviate some meeting costs.

Applicants must be 2016 members by the October 1, 2015 abstract deadline, presenting or senior author on an abstract submitted for the Annual Meeting, and must be actively seeking funding.

For more information about Bridging Funds and the other travel awards, visit the Travel Awards page.

Cholesterol: More Than Just Heart Attacks

When most people hear the word “cholesterol,” they think about their diet, heart disease, and statins. In fact, cholesterol is also an essential component in the membranes of your cells, the biosynthesis of which evolved in reBPJ_109_5.c1.inddsponse to the appearance on earth of an oxygen rich atmosphere, roughly two and a half billion years ago.

So what does cholesterol do for your cell membranes? It has been known for many years that cholesterol organizes and orders the fatty acid component of the membrane, leading to a thicker and more tightly packed lipid bilayer. This makes the membrane more effective as a barrier against ions, water, and other small molecules. However, the biophysical details responsible for this behavior have remained largely unknown.

The cover image shows a configuration sampled by a molecular dynamics simulation of a mixture of two lipids and cholesterol, modeled in all-atom detail. The hydrocarbon chains are rendered in red (a sphingolipid) or blue (a monounsaturated phospholipid). Cholesterol is rendered in yellow.  The shapes of the lipids reflect the details of local packing and order. In the more yellow and red region (cholesterol and sphingolipid rich), the chains of the sphingolipid tend to pack tightly into local hexagonal arrays. Though locally hexagonal, this phase is still fluid, and hence referred to as “liquid-ordered.” In the more blue region (richer in unsaturated chains), the lipids are more loosely packed, and are rendered as Voronoi polygons. The corners of the polygons are smoothed by Bezier splines to evoke the softness of the more fluid, “liquid-disordered” phase. The heights of the polygonal solids are the relative heights of the lipids, revealing that the thickening effect of cholesterol is very local. The image was rendered using the Tachyon ray tracing software.

More simulations like this are sure to follow, with ever more complex lipid mixtures. With high-precision models and careful simulation protocols, these efforts will reveal how compositionally complex membrane mixtures conspire to organize for functional ends, such as signaling and trafficking. Whatever is revealed, it is clear that cholesterol will play a leading role.

—Edward Lyman, Alexander Sodt, Richard Pastor

Egelman’s Culinary Lab: Grilled Chicken Thighs

If you read the profile of BPS President Edward Egelman in the BPS Newsletter earlier this year, you know that in his spare time, he is an avid cook.  We have asked him to share a recipe with readers here.  In keeping with the end of summer in the US, Egelman has chosen to share a grilled dish.

Grill-clipartAfter being asked to contribute a recipe to this blog, I realized how hard it is to choose one particular dish when I am constantly experimenting with food (at home, that is, and not in the lab!). My son, a computer scientist at Berkeley, introduced me to xanthum gum, which is now a staple in modernist cuisine (or molecular gastronomy). It turns out that this polysaccharide has been mainly used in industrial applications, such as thickening mud for oil drilling, and the total production of it exceeds 30,000 tons a year. It gets its name from the bacterium that produces it, Xanthomonas campestris, which uses it for adhesion to plant cells. Since this is the Biophysical Society (and not a cooking blog) I can add that this hydrocolloid is built from pentasaccharides, with a typical molecule having ~ 7,000 pentamers. It is tasteless, and has amazing thickening properties, leading to sauces with a texture that cannot be achieved with other thickeners, such as flour or corn starch. I might also add that biopolymers of all sorts will be the focus of the Thematic Meeting that we are holding in Rio de Janeiro at the end of October, “Polymers and Self-Assembly: From Biology to Nanomaterials.”

The other night I grilled six boneless chicken thighs, tossed with fresh rosemary, salt, pepper, and olive oil. While they were grilling I sautéed a whole diced onion in olive oil. I then added 200 ml of chicken stock (I typically make ~ 30 liters of this at a time, so it is always available in my freezer). This was seasoned with salt and pepper and reduced over very high heat to perhaps half the original volume. I then added ~ 30 ml of cream (two tablespoons), about the same quantity of a good Dijon mustard, and a small pinch of xanthum gum (perhaps 150 mg, but who has a precision balance in the kitchen?). I pureed this with an immersion blender, necessary to fully dissolve the xanthum gum. If you do not have an immersion blender a regular blender would be fine.  The chicken thighs and the sauce were kept warm while I finished the kale. I had previously blanched in boiling salted water perhaps two liters of fresh kale leaves. These were only boiled for about a minute, and then rinsed in very cold water until cool. They were then squeezed quite thoroughly in a colander to remove all water. To finish, the kale was sautéed in olive oil to which some chopped garlic and jalapeños had been added.

The presentation was simple: spread the kale leaves on a warmed plate, place one or two (depending upon the size of the thighs, the number of other courses, and the appetite of the recipient) chicken thighs on top, and then pour the sauce over the chicken. A sprig of fresh rosemary on top of the thigh is all this now needs. Bon appétit!

-Edward Egelman

Feeling for Filaments

BPJ_109_4.c1.inddThe cover image on the Biophysical Journal issue released August 18, 2015 features a live cultured endothelial cell that was imaged using two different techniques: The green fluorescence part was recorded with an optical confocal microscope and displays actin filaments inside the cell in a maximum intensity projection.  The greyscale square shows a shaded visualization of the sample surface as probed by atomic force microscopy (AFM).

The AFM is capable of ‘feeling’ the rigid structures of the cortical cytoskeleton through the cell membrane, hence the rough appearance of the cell’s surface. We developed a technique to image this cortical cytoskeleton web with high resolution and quantify its density. This enables us to observe dynamic behavior and study the effects of pharmacological treatments. Simultaneous confocal fluorescence microscopy enhances the method in terms of molecular labeling; it both allows correlation with AFM data and completes the three-dimensional view of the cell towards the basal side.

Our aim is to elucidate the link between the structure of the cortical actin cytoskeleton, cell mechanics, and physiology. The research in vascular endothelium is inspired by findings on how cell mechanics determine endothelial function. Thus it deals with the pathophysiological background of hypertension and other cardiovascular diseases. Another application can be found in oncogenesis and metastasis, where cell mechanics are also altered.

Our paper is also, hopefully, an interesting read for anyone using AFM in other cell imaging applications because of the methodological issues it addresses: Force stability with uncoated cantilevers, contact-mode versus newer, fast force mapping modes, image processing to extract and segment features on large scale objects, and more.

More information on the endothelial physiology research, AFM mechanobiology and microscopy applications can be found on our website.

–Cornelius Kronlage, Marco Schäfer-Herte, Daniel Böning, Hans Oberleithner, and Johannes Fels

Thoughts after the 2015 BPS Thematic Meeting in Taipei

Following the Biophysical Society’s New Biological Frontiers Illuminated by Molecular Sensors and Actuators thematic meeting held in Taipei, Taiwan this June, student attendee Wen-Ting Yang shared her thoughts on the meeting and her experiences.

“One cannot make bricks without straw,” which came into my mind after this Biophysical Society (BPS) thematic meeting. Consistent with the saying, we can hardly discover the novel frontier of life or build upon the milestones of scientific research without proper methods and materials.

First of all, thanks to BPS. This thematic meeting was well-organized. It deeply discussed the topic, “new biology frontiers illuminated by molecular sensors and actuators,” from five aspects, which provided a clear picture for future research direction in this field.

As a PhD student, this was my first time to take part in an international conference like this by myself. For me, in this conference that was in such a different field from mine, it was really inspiring and frustrating at the same time. How I usually do my research is to basically find out if there is anything new to apply in my experiments for problem solving. However, all the scientists I met at this conference were doing their research in an opposite way. They devoted themselves to inventing and creating something novel and incredible to solve the existing problems and even potential future problems. Without the methods and materials they’ve found and are using, barely can I continue my studies. That was a huge shock to me.  Now, when facing an obstacle, all I can do is search and wait for the appearance of solutions; however, these scientists are able to create the solutions by themselves.

I hope I can be someone like them in the future: To be on the initiative instead of being passive. It was a really great opportunity to participate in the conference. I learned a lot from people in this meeting, not only through their scientific knowledge but also from their humble and respectful attitude toward the living world. I truly appreciate all the people that organized and those who participated in this conference, and also my advisor who encouraged me to join this amazing meeting.

Cell Arrangement and Polarization are Guided by the In-plane Stresses

BPJ_109_3.c1.inddHow did you compose this image?

This image is intended to show how the rigidity of patterned substrate influences the collective arrangement and polarization of cells. Although it is thought that cell arrangement and polarization in pattern formation are regulated primarily by spatial gradients of chemical factors known as morphogens, this image and our article demonstrate that the mechanical factors also play crucial roles. The panels in the first and second rows are the phase contrast images and associated fluorescence images of actin, respectively, which were obtained from our experiment directly. The panels in the third row are schematic illustrations of cell polarization and alignment corresponding to the phase contrast images and the fluorescence images, which are produced by using CorelDraw software (http://www.coreldraw.com/).

How does this image reflect your scientific research?

The cover art image shows that cell polarization and alignment exhibit distinct features on the ring pattern of three different substrate stiffnesses, i.e., 60kPa gel, 40kPa gel, and 10kPa gel from right to left columns. Note that cells prefer to align along the direction of maximum principle stress, particularly on the pattern with highest and intermediate stiffness. Interestingly, these stiffness-dependent cell behaviors (alignment and polarization) exhibit a biphasic feature: Cells had less polarized morphology on both the softest and stiffest substrate, but adopted more polarized morphology on the one of intermediate stiffness. Meanwhile cells more preferentially aligned along the circumferential direction on the substrate of intermediate stiffness than on the ones of the highest and the lowest stiffness. Moreover, we found through mathematical modeling that these enigmatic biphasic behaviors were driven by the in-plane maximum shear stress in the cell layer.

Can you provide an example of how your research might lead to, or be used in, a real-world application?

Pattern formation is an indispensable requirement for the process of tissue morphogenesis. Understanding the mechanisms of pattern formation is crucial for tissue engineering, which allows people to control and regulate the growth of artificial tissue or organs. Our study may provide powerful tools for a precise control of the pattern formation in tissue engineering for potential biomedical applications.

Do you have a website where our readers can view your recent research?

If you are interested in our research, please visit our website: http://www.biomechanics-bit.cn/English/Default.aspx.

– Shijie He, Chenglin Liu, Xiaojun Li, Shaopeng Ma, Bo Huo, Baohua Ji

Rheumatoid Arthritis and Biophysics

July has been designated Juvenile Arthritis Awareness Month by the Arthritis Foundation. NIAMS estimates that about 294,000 American children under age 18 have arthritis or other rheumatic conditions. The Biophysical Society is taking this opportunity to highlight how advances in basic research contribute to our understanding of this disease. We spoke with BPS member Christine Beeton, Baylor College of Medicine, about her research related to rheumatoid arthritis, the most common form of arthritis in children. Her work focuses on targeting potassium channels for the treatment of chronic diseases including multiple sclerosis, rheumatoid arthritis, and type 1 myotonic dystrophy, and using antioxidant nanomaterials for the treatment of T lymphocyte-mediated autoimmune diseases (multiple sclerosis and rheumatoid arthritis).

What is the connRA-FLS bright fieldection between your research and arthritis?

The term arthritis encompasses a number of diseases that affect joints; my focus is on rheumatoid arthritis (RA) that is characterized as a systemic inflammatory and chronic disease. In the last decades the role of resident joint cells, the fibroblast-like synoviocytes (FLS), has come to light in this disease. However, no therapeutic currently specifically targets these cells. We have identified KCa1.1 (BK, KCNMA1) as the major potassium channels at the plasma membrane of FLS isolated from patients with RA and have shown that blocking this channel inhibits pathogenic functions of FLS ex vivo and reduces the severity of two animal models of RA (Hu et al. J. Biol. Chem. 2012; Tanner et al. Arthritis Rheumatol. 2015). We are currently investigating the roles of these channels in the pathogenic functions of FLS and also as a potential target for therapy.

Why is your research important to those concerned about arthritis?

Current therapeutics for RA have significantly improve the wellbeing of the patients. However, most induce immunosuppression and therefore place the patients at risk for infections and tumor development. Our ability to target FLS has the potential of development effective treatments for RA that do not immunocompromised the patients. In addition, targeting both immune cells and FLS by combination therapy may offer the added benefit of using reduced amounts of drugs if the effect is synergistic.

How did you get into this area of research?

During my PhD in Immunology, I had the opportunity to study Kv1.3 channels in T lymphocytes, cells involved in autoimmune diseases. As a student my work focused on multiple sclerosis but as a postdoctoral fellow I extended this work to RA. When testing Kv1.3 blockers in animal models of RA and analyzing potassium channel expression in synovium biopsies from patients with RA I became interested in the potassium channel phenotype of other cells involved in RA. When I started my own laboratory I started a collaboration with Dr. Gulko, a rheumatologist now at Mount Sinai in New York, and focused my attention to FLS. This lead to the identification of KCa1.1 as the major potassium channel at the plasma membrane of these cells.

How long have you been working on it?

I started working on potassium channels in FLS from patients with RA in 2008, soon after starting my laboratory at Baylor College of Medicine.

Do you receive public funding for this work? If so, from what agency?

This work is not funded by the NIH but we have received funding fromX-rays the Alkek Foundation for Medical Research and from Baylor College of Medicine.

Have you had any surprise findings thus far?

Many. The happiest was to find out that FLS from patients with RA express one major potassium channel at their plasma membrane and not a combination of many channels, which would have made the work of identifying them and defining their roles a lot more complicated. The most puzzling was the finding, repeated many times, that blocking KCa1.1 induces a calcium transient in these cells. This really intrigued us and started us into studying the cell signaling downstream of the channel.

What is particularly interesting about the work from the perspective of other researchers?

Over the last few years, FLS have emerged as important players in the pathogenesis of RA. While many signaling molecules have been identified as regulators of various pathogenic functions of these cells, nothing was known about the expression and function of potassium channels. Our work therefore brings a new cell signaling regulator to light.

What is particularly interesting about the work from the perspective of the public?

Getting a better understanding of the different cell types that play a role in rheumatoid arthritis will help design better drugs to combat this disease. In addition, understanding the roles of KCa1.1 channels in the function of FLS during RA may help understand the roles of these and other potassium channels in other tissues and diseases.

Do you have a cool image you want to share with the blog post related to this research?

I am showing two cool images; one of an FLS, isolated from the joint of a patient with RA who had to undergo therapeutic joint surgery due to disease severity. The other shows X-ray images of the hind paws of rats with a model of RA induced by the injection of pristane. In the top X-ray, joint damage (yellow arrows) is visible; In contrast, the joints are much healthier in the paw of the rat that was treated with a KCa1.1 blocker for 21 days, starting at onset of clinical signs.