April 24, 2014

I’m still waiting for my miniaturizing spaceship* so I can dive into a cell with my dog and ride in the lamella of a crawling cell. Until then, I will gladly enjoy images like today’s, from the Lippincott-Schwartz lab.

A cell’s shape can change for many reasons, including crawling, tissue regeneration, and cancer progression. Cell shape is dynamic, relying on temporal and spatial coordination of several processes. The three-dimensional nature of cell shape, however, presents a challenge for microscopists. By using structured illumination microscopy (SIM), Burnette and colleagues created images of the three-dimensional organization of actin filaments. From these 3D superresolution analyses in crawling cells, Burnette and colleagues found a contractile network of actin filaments at the top of a crawling cell, organized like muscle sarcomeres. Their model of balanced contraction and adhesion helps to guide further investigations of cell shape changes in healthy and diseased tissue. The image above shows actin filaments at color-coded heights within a crawling cell. The closed arrow points to actin at the top of the cell.

*My birthday is next month, if anyone is wondering about gift ideas.  

Burnette, D., Shao, L., Ott, C., Pasapera, A., Fischer, R., Baird, M., Der Loughian, C., Delanoe-Ayari, H., Paszek, M., Davidson, M., Betzig, E., & Lippincott-Schwartz, J. (2014). A contractile and counterbalancing adhesion system controls the 3D shape of crawling cells originally published in the Journal of Cell Biology, 205 (1), 83-96 DOI: 10.1083/jcb.201311104

January 17, 2013

Membranes have to wear many hats. A cell’s plasma membrane must be sturdy enough to protect the cell, yet fluid enough to support the cell’s dynamic and swingin’ lifestyle. A recent paper hypothesizes how plasma membranes can accomplish both tasks, and provides beautiful images and results to show this fascinating life of a membrane.
 
A cell’s plasma membrane protects and contains the contents of the cell, but is also flexible and fluid enough to allow the many events that take place at or involve the membrane, such as cell migration and changes in cell shape. A recent paper presents a mechanism for how a plasma membrane can accomplish both structure and flexibility. Kapustina and colleagues monitored rounded cells and the periodic membrane protrusions they make, and found compression (folding) and dilation (unfolding) of the plasma membrane and underlying actin cortex during protrusion events. This compression-dilation mechanism allows the cell to make rapid changes in cell shape, and can produce amoeboid-like migration movements under certain conditions. The electron microscopy images above show a cell fixed during membrane oscillations. Membrane folding appears as finger-like or round projections. (The yellow box shows the position of the higher magnification image on the right; red arrows point to dense cortical regions.)

BONUS!!  Beautiful movie of F-actin (green) and myosin (red) during membrane protrusions is below.  More movies of these membrane dynamics can be seen here.

 Kapustina, M., Elston, T., & Jacobson, K. (2013). Compression and dilation of the membrane-cortex layer generates rapid changes in cell shape originally published in the Journal of Cell Biology, 200 (1), 95-108 DOI: 10.1083/jcb.201204157

June 11, 2012

If you invited a protein to a party, it’d win your Twister tournament without a doubt. A protein is not just some static stick of cellular function, but can be a complicated structure that bends or twists in three dimensions and can interact with other domains (of itself or another protein). Today’s image is from a paper describing a thorough analysis of one domain on a Shroom protein.

Shroom (Shrm) proteins play important roles throughout development. Through their interaction with Rho kinase (Rock), Shroom proteins regulate the localization of the actin-myosin contractile network, which in turn affects cell and tissue shape. A recent paper describes a specific domain of Shrm, the SD2 domain, and its importance in the interaction between Shrm and Rock. In this paper, Mohan and colleagues present the structure of the SD2 domain and show the specific amino acid residues on the protein that are necessary for Shrm-Rock interaction, both in vertebrates and invertebrates. In the images above, mammalian cell cultures are treated with different Shrm SD2 constructs. Intact SD2 domains for both mouse (top) and fruit fly (middle) were able to constrict the cells expressing the construct (green cells). Without the SD2 domain (bottom), cells were unable to constrict.

Mohan, S., Rizaldy, R., Das, D., Bauer, R., Heroux, A., Trakselis, M., Hildebrand, J., & VanDemark, A. (2012). Structure of Shroom domain 2 reveals a three-segmented coiled-coil required for dimerization, Rock binding, and apical constriction Molecular Biology of the Cell, 23 (11), 2131-2142 DOI: 10.1091/mbc.E11-11-0937

May 16, 2011

No cell is an island. Cells are influenced by their environment around them, and migrating cells are especially receptive to the surface they are crawling over. Today’s image is from an elegant study on how different forces regulate cell shape and movement.

Cell migration is a highly coordinated process that depends on many factors. One of these factors is the cell’s adhesion to the underlying substrate, and a recent paper clearly spells out how the adhesion strength of a substrate directly affects a migrating cell’s shape and motility. In the images above, migrating cells were placed on surfaces of different adhesion strength. Cells crawling with either low or high adhesion are slow and round compared to cells crawling on surfaces with medium adhesion strength. These alterations in adhesion affect the localization of actin (top, red) and the actin motor myosin (middle, green).

Barnhart, E., Lee, K., Keren, K., Mogilner, A., & Theriot, J. (2011). An Adhesion-Dependent Switch between Mechanisms That Determine Motile Cell Shape PLoS Biology, 9 (5) DOI: 10.1371/journal.pbio.1001059

March 3, 2011

When I first learned about the elegant experiments of the late Ray Rappaport, I remember feeling like I was having a Zen moment. Amazing things can be learned from some of the simplest experimental designs, and this is a very calming and satisfying concept. Today’s image is from a paper using those same sea urchin eggs that Rappaport used*, and provides us with a great prediction tool for determining how a cell will divide.

Many cells in an embryo must divide in a certain orientation, and many biologists have tried to make predictions on how this orientation is determined. Add the varying shapes a cell may take on within a developing organism, and making these predictions is less than straightforward. In order to make predictions on cell division orientation, a group of biologists set sea urchin eggs into wells of varying shapes. By monitoring the cell division axis in many cells set in wells of many shapes, Minc and colleagues developed a computational model that predicts how the cell division axis is determined for any given shape. Images above show sea urchin embryos in wells of different shapes.

Minc, N., Burgess, D., & Chang, F. (2011). Influence of Cell Geometry on Division-Plane Positioning Cell, 144 (3), 414-426 DOI: 10.1016/j.cell.2011.01.016
©2011 Elsevier Ltd. All rights reserved.

* Correction: Rappaport didn't use sea urchin eggs. In most of his experiments, he used a different echinoderm--the sand dollar. Thanks to Bob G. for the note!

December 13, 2010

It is always exciting to read a paper that describes a fascinating discovery. It is even more exciting when that discovery opens the door to so many interesting questions. The paper that brought us today’s image is a great example of this.

When biologists look at cells growing on a culture dish, the cells are usually rounded blobs. Recently, a group of cell biologists had cells grow along lines in a culture dish to examine cell elongation. Regardless of cell size, all of the cells reached similar lengths. The intrinsic “ruler” that limits the length is a population of dynamic microtubules that grow along the side of the cell during elongation, and the authors suggest that this mechanism may play a large role during development. Images show microtubules in a control cell (left) and cells grown along an adhesive line (right) at different time points after attachment. The microtubules in the elongating cells become polarized and grow along the long sides of the cells.

Picone R, Ren X, Ivanovitch KD, Clarke JD, McKendry RA, & Baum B (2010). A polarised population of dynamic microtubules mediates homeostatic length control in animal cells. PLoS biology, 8 (11) PMID: 21103410

September 9, 2010

The protein spectrin is found at the cell’s plasma membrane and serves to provide shape and stability to a cell. In addition to serving as part of a cell’s scaffolding network, spectrin has also been assigned functions in cell polarity and membrane traffic. A recent paper has looked at the requirement for spectrin, and its adaptor protein ankyrin, in neurons and other cells in the fruit fly Drosophila. Image above shows two salivary glands with normal (left) or increased (right) levels of spectrin. Too much spectrin in this tissue leads to changes in cell shape and polarity.

Reference: G. Harper Mazock, Amlan Das, Christine Base, and Ronald R. Dubreuil. Authors’ Molecular Biology of the Cell paper can be found here.