The amoeboid movement by which many types of cell crawl across surfaces has fascinated scientists ever since it was first observed using the earliest microscopes. Until recently, it has remained mysterious how cells extend the thin protrusion, known as a lamellipod, that enables them to move forward. In the past decade, however, extensive experimental work has shown that amoeboid motility is associated with the regulated polymerisation of branched actin filaments within the lamellipod.
Now, researchers at the London Centre for Nanotechnology and in Cambridge have developed a physical model that explains how this polymerisation generates motion. In a paper published in Proceedings of the National Academy of Sciences, Christian Schreiber (Cambridge University), Murray Stewart (MRC Laboratory of Molecular Biology) and Tom Duke (LCN) propose that the key point is that the packing efficiency of randomly oriented rod-like filaments decreases rapidly as the filaments get longer.
Actin branches are nucleated on existing filaments by a protein complex called Arp2/3. According to the model, Arp2/3 is activated only when it is bound to a factor that resides in the highly curved section of the membrane at the leading edge of the lamellipod. The growing filaments then diffuse away from the membrane but soon get entangled with other filaments, forming a jammed network of stiff rods. As the filaments continue to grow, the network has no option but to swell. The horizontal component of the expansion propels the leading edge of the lamellipod forwards, while the upwards component sets the characteristic height of the lamellipod, which is typically about 200nm. The model explains, for the first time, how the speed of propulsion varies when a force is applied to the front of a cell to restrain its motion.
This new insight will be invaluable in the study of a wide variety of biological processes in which amoeboid cell motility is important, including the development of the nervous system, wound healing and cancer metastasis.
Journal link: [PNAS early edition]
Figure 1: Simulation of the dynamic mesh of branched actin filaments within a lamellipod