Saturday, November 22, 2008

How do Cells Crawl?

From Scienceblogs:
There are so many great stories waiting to be discovered when you approach biology from the view point of the cell. Remember a cell is the smallest unit of life. You cannot divide it further and obtain an entity capable of reproduction and self-renewal. The cell is when chemistry meets biology. Look at every major research institution and there are loads of people working on problems involving cells, in fact there are probably more people studying cells then there are people studying physics and chemistry combined. And the problems addressed by cell biology are the very essence of basic research.

How do cells talk to each other? How do they divide, how do they KNOW when to divide? How do cells commit suicide? How do cells monitor their size, levels of energy, amount of metabolites? What do all of these processes have to do with cancer?

Perhaps one of the most fascinating stories that would be excellent fodder for an article aimed at the lay reader would be how do cells crawl. There is something primal about motion, this process is central to life and it is incredible that a bag of molecules can manage to crawl around towards and away from cues found in the environment that surrounds them. Think of it, a cell is nothing but a bag, densely packed with all sorts of bizarre machines and filaments that act together in concert to propel a cell forward. The writer countered that such an article would describe how protein A binds to protein B that then adds a phosphate to protein C ... and reading the primary literature you would think hat that is all there is. But I have to say that this type of analysis is comparable to describing how a car operates by analyzing every nut and bolt. Biology after all is the study of minutia, and there are so many details that the only way to study cell biological processes is to dissect it down. Very rarely do you have one paper describing a novel finding in cell biology that encapsulates the whole process. You need to immerse yourself in the literature, talk to people doing the work, and all of a sudden a larger picture develops. At that point you realize that there is a better way of describing a motile cell, just like there is a better way of describing how a car works by using broader concepts.

It involves broader concepts such as the flow of actin filaments, the power of myosin motors, and the cellular clutch which involves these huge structures called focal adhesions that mediate interactions between the actin and the solids that are found on the exterior of the cell. To really describe the interior of a cell, we need to temporarily ditch the car metaphor and switch to something much more dynamic the activity inside of a motile cell is comparable to a ocean tide of actin meshwork. Actin filaments are assembled right underneath the leading edge of the motile membrane and are swept back to the rear of the cell by myosin motors. This tidal wave pushes everything including the nucleus towards the back of the cell. The actin meshork then collapses and is contracted together into long filaments called stress fibers. To generate traction the actin is hooked upto these large focal adhesions that line the sides of the membrane and help the cell cling to solids from the outside. The attachment transforms the rearward motion of actin into a forward push on the leading edge. Yes I've just described a clutch - and with that w move back to the car analogy.

At this point you can end the piece. But there is much more. It turns out that this actin flow and the molecular machine that generates it can be found in almost any cell that is responding to some extracellular stimulus The core components of this biological process are used by almost every single eukaryotic cell that wants to change its shape, whether it be a crawling amoeba, a migrating neuron, a budding yeast or even a plasmodium invading a red blood cell. In fact these components accomplish a much more basic task than allowing for cell to move or simply to change shape, this ancient machinery allows cells to reorganize their inner structure in response to a cue coming from one discrete point on its periphery. This process is called cell polarization.
I didn't know that cells crawl. It is really humbling - and scary sometimes - to realize how little I know.

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