Cell migration is soooo cool

In the Februray 6th issue of Cell there is an indept study by the Borisy & Sheetz labs that describes how crawling cells push and ruffle and bend the membrane at the very front with the aid of actin dynamics. Very cool stuff, very cool movies. I'll blog (or attempt to blog) about the actual paper in the near future. For today I have some background on actin dynamics in migrating cells.

Just to remind you what we're talking about, here is a movie of a migrating keratinocyte (skin cell) from the Borisy lab webpage.

Note that at a certain point the cell is fixed and lysed. We then zoom into an image of the same cell but as seen through an electron microscope. As we focus in we can start to see the actin meshwork right at the cell's leading edge. Subunits of actin are added to the plus end of these filaments which point to the top of the micrograph, towards the membrane. At the end of the movie the actin branches, with a characteristic 70 degree branching pattern, are pseudo-colored in yellow. These are generated by the Arp 2/3 complex which binds to the side of a preexisting actin filament and nucleates a new filament that grows at a 70 degree angle from the older filament. An exanple of a single branch can be seen at the very end of the movie ("S1" labels the directionality of the actin filament).

Now previously I described the two main actin driven structures found in a migrating cell.

1) The lamellipodium, which is generated by a rapid polymerization of actin just bellow the leading edge and is responsible for pushing out onto the membrane and determining the directionality of locomotion. This structure is generated by Arp2/3 mediated polymerization of actin. The addition of actin monomers to the meshwork found right under the membrane (see the movie above) act as a Brownian ratchet to push membrane forward. As this steady stream of actin is added right at the front, the actin meshwork is being pushed backwards. It's thought that the lamellipodium function is to probe the environment just ahead of the migrating cell. Thus it's role is to determine which direction the cell should migrate.

2) The lamellum, which is found closer to the cell body (i.e. between the lamellipodium and the cell center). In this region the actin meshwork is transported away from the leading edge towards the cell interior by the motor myosin II. In comparison to the retrograde movement of actin in the lamellipodium, this second rearward actin movement is much slower. As I described previously, it is thought that this part of the cell is most likely generating most of the force that propels the cell forward.

If you look realy closely at the movie from the Borisy lab you can see that the lamellipodium has a "denser" actin meshwork than the lamellum. There are other molecular differences as well. Cells make very small attachments to the extracellular environments in the lamellipodium, called focal contacts. These structures become much bigger and are called focal adhessions in the lamellum. Focal adhessions are usually attched to large actin cables and are major sites for cellular signalling. For more on actin structures, see this post.

But lets get back to that meshwork and the lamllipodium/lameelum. By injecting low concentrations of fluorescent actin into cells, researchers can label the actin meshwork and examine its bulk properties. Here is a movie from Claire Waterman-Storer's lab page that images such a cell and demonstrates these two actin "zones".

Notice the quick rearward movement of actin right at the front in the lamellipodium and the slower retrograde movement in the rest of the cell (the lamella). In my next post I'll talk about the Cell paper.