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Soft Matter Physics Division - Biophysics at the University of Leipzig University of Leipzig
IntroductionCell Motility
 
 
Directed cell migration accompanies us from conception to death. This integrated process choreographs the morphogenesis of the embryo during development. The failure of cells to migrate or migration of cell to inappropriate locations can result in life threatening consequences such as the congenital defects prominent in the brain. In the adult, cell migration is central to homeostatic processes such as mounting an effective immune response and the repair of injured tissues. It contributes to pathologies including vascular disease, chronic inflammatory diseases, and tumor formation and metastasis. Understanding cell migration is also becoming important to emerging areas of biotechnology which focus on cellular transplantation and the manufacture of artificial tissues. In the following we will discuss cell motility in Homeostasis as an example of cell motility. Some basic migration mechanics will be given.
 

Homeostasis
 
 
(Movie is Copyright to the Cell Biology and Cytoskeleton Group at Harvard.)
Immunity and wound healing are two homeostatic processes in the body that rely on the ability of cells to migrate. Neither of these processes would be possible if it were not for migration, and often they occur together. For example, when you cut yourself, the process of wound healing is initiated to repair the damage. Cells of the immune system are recruited to dispose of invading bacteria and other microorganisms entering through the wound. Cells proliferate and migrate to fill the wound. If bacteria opportunistically entered through the wound, white blood cells (leukocytes) from the circulation migrate into the surrounding tissue to destroy them. The bacteria are engulfed by the white blood cells, where potent digestive enzymes destroy them. Immune cells are constantly on surveillance duty, circulating throughout the body looking for foreign material to attack and destroy, and thus it is important for these cells to develop a sense of self so that they can recognize the bodies own cells and not destroy them. This sense of self is established early on in their development as they migrate through the primary lymphoid tissues of the bone marrow and thymus. On the rigth you can watch a movie of a human polymorphonuclear leukocyte (neutrophil) on a blood film, crawling among red blood cells, notable for their dark color and principally spherical shape.The neutrophil is "chasing" Staphylococcus aureus microorganisms, added to the film.
 

Basic Migration Mechanics
 
 
(Figure by Revathi Ananthakrishnan & Allen Ehrlicher, published in [R. Ananthakrishnan, A. Ehrlicher: The Forces Behind Cell Movement, Int. J. Biol. Sci. 3:303-317 (2007)])
Migration is a dynamic, cyclical process in which a cell extends a protrusion in direction of motion by actin polymerization at the leading edge (see figure on the right). It then adheres its leading edge to the surface on which it is moving via focal adhesions and de-adheres trailing edge of the cell. Finally, it pulls the whole cell body forward by contracile forces generated at the cell body and rear of the cell.
This cycle is initiated by external signals (chemotactic molecules), which are sensed and communicated to the cell's interior by specialized receptive proteins in the cell membrane. In response to these signals, cells extend protrusions, by polymerizing actin, that act as feelers, seeking out new terrain and sensing the direction from which they are receiving signals. Once the direction for movement is established the machinery for enabling movement assembles with regard for the direction of migration. Adhesive complexes needed for traction collect at the front of the protrusion, tethering the protrusion to the substratum. Actomyosin filaments contract at the front of the cell and pull the cell body toward the protrusion. Release of adhesive connections in the rear of the cell and retraction of the tail completes the cycle. The orchestration of this complex process resides in many molecules that serve to distinguish the front from the rear of the cell and whose actions are carefully timed.

This movement process can be observed at a small movie of a crawling Fibroblasts. The F-actin in the lamellipodia is GFP-Actin fluorescence labled and thus visible. Click here.

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