January 29, 2014

The term “pathogen propulsion” sounds like an awesome technique for defeating the evil squid overlords. In fact, a lot of concepts involving propulsive actin comets sound awesomely science fictional, but thankfully they are not. Today’s image is from a paper describing how several viruses use actin comet tails to propel themselves to other cells.

Several pathogens such as baculovirus, Listeria, and Shigella hijack their host cell’s own actin cytoskeleton in order to propel themselves into other cells and spread infection. Behind each pathogen is a comet made of actin filaments and associated actin regulators, but the mechanism of propulsion and the structure of the actin comet have been debated. A recent paper in PLoS Biology by Mueller and colleagues describes the use of electron tomography to show a fishbone-like array of actin filaments behind baculovirus, the smallest pathogen known to use propulsive actin comets. These comets use an average of four actin filaments at any one time to propel the virus. Using these results, the researchers ran computer simulations that support a model of propulsion in which actin filaments are continuously tethered to the pathogen. The image above shows a negatively-stained actin comet tail behind a baculovirus particle (BV), and the 3D projection of the image shows branch points of the actin tail as red dots. Insets in top image show details of the branch points, and grey tube is a microtubule.

BONUS! Below is a movie of baculovirus propelling itself around a cell. Virus particles are red, and actin comet tails can be seen in green behind the particles.

Mueller J, Pfanzelter J, Winkler C, Narita A, Le Clainche C, et al. (2014) Electron Tomography and Simulation of Baculovirus Actin Comet Tails Support a Tethered Filament Model of Pathogen Propulsion. PLoS Biol 12(1): e1001765. doi:10.1371/journal.pbio.1001765.

January 22, 2014

The C-word is a dirty, dirty word that every single person dreads hearing. Cancer touches every family at some point (or so it seems), so the effort put forth to finding a “cure” for cancer is huge. Today’s image is from a very exciting paper that shows how specific cells in a breast tumor lead the charge towards invasion. 

The spread of cancer, or metastasis, can occur either through the invasion of single tumor cells into nearby tissue or by collective invasion of several cells as a cohesive unit. A recent paper from Andy Ewald’s lab at Johns Hopkins describes the identification of cells involved in collective invasion, using a 3D assay of primary breast tumors invading other tissue. Kevin Cheung and colleagues found that in mouse breast cancer models and diverse human breast tumors, the cells leading the invasion charge are distinct from the bulk tumor cells, and express the basal epithelial genes cytokeratin-14 (K14) and p63. Additionally, knockdown of either K14 or p63 could block collective invasion in advanced carcinomas. In the images above, leading invasive cells express K14 (middle image, green) and are distinct from the bulk of the mouse mammary tumor.

BONUS!! For a great “Out of the Box” description of these very cool results, click here.

Kevin J. Cheung, Edward Gabrielson, Zena Werb, Andrew J. Ewald (2013).  Collective Invasion in Breast Cancer Requires a Conserved Basal Epithelial Program.  Cell, 15 (7), 1639–1651. http://dx.doi.org/10.1016/j.cell.2013.11.029  Copyright ©2013 Elsevier Ltd. All rights reserved.

January 15, 2014

The mitotic spindle seems to get all the fun of a microtubule-dynein party, but do not fret. A recent paper describes some cool interactions of microtubules with dynein at the cell’s cortex.

The molecular motor dynein walks along microtubules, and this movement can do great things by moving the microtubules themselves or moving material along the microtubule. Recent work found that dynein at the cell’s cortex may influence cell motility using an actin-independent mechanism that pushes microtubules along the cortex. In an even more recent paper in the journal Molecular Biology of the Cell, this same research group shows these cortical dynein-microtubule interactions directly. Using TIRF microscopy, Mazel and colleagues found speckles of cortical dynein complexes associated with microtubules. These microtubules can move, bend, and even rotate around these speckles. The images above show the difference between wide-field microscopy (left) and TIRFM (right) when imaging microtubules at the cortex. In the bottom panel, a short microtubule can be seen moving directionally.


Tomáš Mazel, Anja Biesemann, Magda Krejczy, Janos Nowald, Olga Müller, & Leif Dehmelt (2014). Direct observation of microtubule pushing by cortical dynein in living cells Molecular Biology of the Cell, 25 (1) DOI: 10.1091/mbc.E13-07-0376

I’mmmm baaaaaack!

I’mmmm baaaaaack!

It’s a new year for HighMag Blog, and it’s about time for me to get back to the wondrous world of cells.

On August 12, I welcomed my second daughter into this world and have been spending my time getting to know her. I have to admit that science has been far from my mind as I’ve tried to figure out how to take care of two little ones, but I’m starting to miss cells and their crazy worlds. Next week, I’ll begin posting images (weekly at first). I look forward to again having my 4-year old gape over my shoulder to ask about the images I’m writing about…no age is too young for a journey into the Alberts et al. cell biology bible.

As in the past, I welcome you to submit your own images for a shot at HighMag glamour. I also welcome suggestions for papers/images that you’ve recently come across that absolutely must have their day in the spotlight. Email me at highmagblog@gmail.com.

A personal note

This will be my last HighMag post for a while, as I await the August arrival of my second daughter.  While I love looking at beautiful images of cells and reading exciting new papers, I am currently obsessed with insane nesting projects…as if the baby will be interested in our how organized our garage is.  After Baby arrives and my sleep deprivation eases up a bit (ha!), I look forward to posting again on HighMag.

To make sure you don’t miss future HighMag posts, be sure to “Like” the HighMag Facebook page.  All of the cool kids are doing it, so you should too.

If you need to contact me for anything, feel free to email me at highmagblog@gmail.com.  

Until I’m back in the HighMag saddle, check out these HighMag Greatest Hits I've compiled for you.  The following are links to posts that were either your favorite images and papers (lots of traffic!) or my own personal favorites.  Enjoy!

2013

http://highmagblog.blogspot.com/2013/01/january-10-2013.html

http://highmagblog.blogspot.com/2013/02/february-19-2013.html

2012

http://highmagblog.blogspot.com/2012/02/february-23-2012.html

http://highmagblog.blogspot.com/2012/03/march-8-2012.html

http://highmagblog.blogspot.com/2012/04/april-5-2012.html

http://highmagblog.blogspot.com/2012/05/may-31-2012.html

http://highmagblog.blogspot.com/2012/08/august-10-2012.html

http://highmagblog.blogspot.com/2012/09/september-18-2012.html

http://highmagblog.blogspot.com/2012/10/october-11-2012.html

http://highmagblog.blogspot.com/2012/10/october-30-2012.html

2011

http://highmagblog.blogspot.com/2011/03/march-3-2011.html

http://highmagblog.blogspot.com/2011/05/may-2-2011.html

http://highmagblog.blogspot.com/2011/05/hooolllly-crap-this-is-so-cool-was-what.html

http://highmagblog.blogspot.com/2011/05/may-26-2011.html

http://highmagblog.blogspot.com/2011/06/june-27-2011.html

http://highmagblog.blogspot.com/2011/08/august-22-2011.html

http://highmagblog.blogspot.com/2011/10/october-17-2011.html

http://highmagblog.blogspot.com/2011/11/november-10-2011.html

2010

http://highmagblog.blogspot.com/2010/02/february-25-2010.html

http://highmagblog.blogspot.com/2010/03/march-1-2010.html

http://highmagblog.blogspot.com/2010/04/april-5-2010.html

http://highmagblog.blogspot.com/2010/09/september-20-2010.html

http://highmagblog.blogspot.com/2010/10/october-14-2010.html

http://highmagblog.blogspot.com/2010/11/november-22-2010.html

July 17, 2013

We don’t need to reinvent the wheel (even if someone tried to in 2001...click here).  We use the wheel for so many things ranging from transport to energy.  Cells have proven clever at co-opting machinery for multiple processes, as the paper from today’s image describes.  This recent paper shows the use of specific machinery in both cytokinesis and neuronal migration.

When neurons migrate, there is a leading process in the front of the cell body and a trailing process.  The leading process contains actin filaments that enable the cell body of the neuron to move forward.  A recent paper describes how the microtubule-based motor kinesin-6 plays an important role in neuronal migration.  Kinesin-6 is best known for its role in cytokinesis, the physical division of a cell after mitosis.  Falnikar and colleagues found that kinesin-6 concentrates in the same region as actin filaments in the leading process of a migrating neuron.  Without kinesin-6, neurons lose their bipolar leading-trailing process morphology, concentrate actin filaments in more than one process, and either remain stationary or continually change the direction of migration.  In addition, Falnikar and colleagues found that kinesin-6 signals through the GTPase activating protein MgcRacGAP to regulate the actin cytoskeleton, as it does during cytokinesis.  In the images above, control neurons (top time-lapse series) moved in a single direction, while neurons depleted of kinesin-6 bottom) frequently changed directions.

BONUS!!  Check out a movie of a wandering, migrating kinesin-6-depleted neuron below.

Aditi Falnikar, Shubha Tole, Mei Liu, Judy S. Liu, & Peter W. Baas (2013). Polarity in Migrating Neurons Is Related to a Mechanism Analogous to Cytokinesis Current Biology, 23 (13), 1215-1220 DOI: 10.1016/j.cub.2013.05.027 Copyright ©2013 Elsevier Ltd. All rights reserved.

July 10, 2013

The grace of a migrating cell is as deceiving as a pair of Spanx on an English Bulldog… there is a lot going underneath.  Today’s image is from a paper showing the importance of the protein vinculin at the leading edge of a migrating cell.

Cell migration is driven by actin filament polymerization that pushes the leading edge of the cell forward, as well as F-actin retrograde flow.  Focal adhesions (FAs) adhere the crawling cell to the underlying extracellular matrix (ECM), and are assembled and disassembled near the leading edge of the cell.  Proteins of these FAs are believed to make up a “molecular clutch” that engages the retrograde F-actin flow, and a recent paper identifies the protein vinculin, an actin-binding protein, as a molecular clutch.  Thievessen and colleagues investigated the effects of vinculin gene disruption in migrating fibroblasts, and found that vinculin is important in regulating F-actin organization and FA dynamics.  Specifically, vinculin generates the ECM traction forces necessary for migration, and promotes FA formation and turnover.  In the images above, a normal fibroblast (top) and a fibroblast lacking vinculin (bottom) show F-actin (green) and the lamellipodial protein cortactin (purple).  Normal crawling fibroblasts have a sharply defined band of cortactin colocalized with F-actin at the leading edge, while vinculin mutants have a wider, less defined region of cortactin at the leading edge, suggesting the importance of vinculin in leading edge organization.

BONUS!  Check out some cool movies from this paper here.

Thievessen I, Thompson PM, Berlemont S, Plevock KM, Plotnikov SV, Zemljic-Harpf A, Ross RS, Davidson MW, Danuser G, Campbell SL, & Waterman CM (2013). Vinculin-actin interaction couples actin retrograde flow to focal adhesions, but is dispensable for focal adhesion growth. originally published in the Journal of Cell Biology, 202 (1), 163-77 PMID: 23836933