November 26, 2014

Patterns are soothing for left-brained folks like me, with the exception being those terrible patterned holiday sweaters that will come out of mothball-ridden closets soon (unsettling for everyone, really). Today’s images are from a paper describing a new micropatterning technique to look at plasma membrane proteins. 

The plasma membrane of a cell is riddled with many multi-protein complexes that facilitate communication and transport. These complexes provide a challenge to biologists due to their ubiquitous localization around the cell, their large, complex size, and their transient interactions with proteins. A recent paper describes a technique to study signaling complexes at the plasma membrane, using micropatterns within the plasma membrane. Löchte and colleagues expressed a protein bait in a micropattern in a living cell’s plasma membrane. Dynamics of the interactions between the protein bait and ligand target can then be quantified using live microscopy and on a single-molecule level. Löchte and colleagues used the IFN interferon signaling complex, using one of the receptor units (IFNAR2) as bait. In the top images above, the micropatterned receptor bait (IFNAR2) was able to recruit the other IFN receptor subunit (IFNAR1, green) after the addition of the ligand (red; time represents the addition of the ligand). Bottom image shows a closer view of the high-affinity, micropatterned binding that requires simultaneous interaction of the ligand (red) with both receptor subunits.

Lochte, S., Waichman, S., Beutel, O., You, C., & Piehler, J. (2014). Live cell micropatterning reveals the dynamics of signaling complexes at the plasma membrane originally published in the Journal of Cell Biology, 207 (3), 407-418 DOI: 10.1083/jcb.201406032

November 19, 2014

You might not be able to get rid of the bad guys, but you can still win the battle if you cripple their mobility. Today’s image is from a paper describing how a tumor’s microenvironment can predict the motility of individual tumor cells.

Metastasis is the spread of cancer cells throughout the body. The motility of tumor cells depends on the microenvironment around them, and a recent paper systematically looks at how that microenvironment can predict or alter the behavior of tumor cells. Gligorijevic and colleagues tracked the motility of individual mouse mammary carcinoma cells in vivo using high-resolution multi-photon microscopy, and found that tumor cells exhibited either fast or slow locomotion. Those tumor cells with slow locomotion also exhibited invadopodia, protrusions that Gligorijevic and colleagues directly link to degradation of the underlying extracellular matrix and metastasis. While no single parameter of the tumor’s microenvironment could predict the locomotion of tumor cells, a support vector machine algorithm indicated how combinations of many parameters could predict tumor cell phenotype and behavior. By characterizing the heterogeneous microenvironment of a tumor and predicting the location and behavior of metastatic tumor cells, researchers can better understand treatment of tumors and the varying responses. Images above show protrusions (arrowheads, over 30 minutes) on two different tumor cells with slow locomotion, with protrusions facing collagen fibers (purple).

BONUS!! Check out a movie of these protrusions below. Note that some protrusion face collagen fibers (purple, panels a and b), and some protrude into blood vessels (red, panels c and d).

BONUS!! Check out Bojana Gligorijevic ‘s interview with SciArt about her images, research, and art here.

Gligorijevic, B., Bergman, A., & Condeelis, J. (2014). Multiparametric Classification Links Tumor Microenvironments with Tumor Cell Phenotype PLoS Biology, 12 (11) DOI: 10.1371/journal.pbio.1001995

November 12, 2014

You might think that the “kiss-and-hop” is a dance move strictly forbidden at a Duggar homeschool prom, but it refers to the quick dynamics of the microtubule-associated protein tau. Today’s image is from a paper describing unexpected results about how tau resides on and regulate microtubules without physically impeding microtubule motors. 

The microtubule-associate protein tau binds to and stabilizes the microtubules within an axon. As most tau is believed to decorate axonal microtubules, it was previously unclear how tau can function in its non-microtubule-dependent roles, or how the presence of tau does not interfere with microtubule motors and axonal transport. A recent paper by Janning and colleagues describes the use of single-molecule tracking of tau in living cells. Janning and colleagues found that tau resides on a single microtubule for 40ms before hopping to the next microtubule, and that this unexpectedly short residence time is sufficient to affect microtubule stability. This “kiss-and-hop” mechanism allows for normal axonal transport, and suggests how some tau functions away from microtubules. In the images above, tau (red) is labeled in mouse cortical neurons, as are microtubules (green) and the nucleus (blue).  

Janning, D., Igaev, M., Sundermann, F., Bruhmann, J., Beutel, O., Heinisch, J., Bakota, L., Piehler, J., Junge, W., & Brandt, R. (2014). Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons Molecular Biology of the Cell, 25 (22), 3541-3551 DOI: 10.1091/mbc.E14-06-1099