Cell motility and the problem of anatomical homeostasis.
The locomotion of tissue cells need not be invasive or disrupt normal tissue geometry, as occurs in cancer. The normal relationship between anatomical structure and cell locomotion is exactly the reverse, with motility serving to create and maintain the structures of the body. This relationship is most extreme in sponges, where time-lapse films show that the cells move about continually in patterns that restructure these animals' simple anatomy. The cells choose their position according to their differentiated cell type, which is the opposite of what is usually assumed to occur in development and has important implications for the functional significance of histotypic cell sorting. A particular type of cellular force that seems to be important in morphogenesis is the traction that all motile tissue cells exert. This traction can be studied by culturing cells on very thin sheets of silicone rubber, so that the locations and variations in the cellular forces are made visible by the wrinkles they produce in the rubber substratum. One finding has been that the traction forces exerted by untransformed fibroblasts are very much stronger than is needed for their own locomotion, but are well adapted for the function of rearranging and aligning collagen fibres to form structures like ligaments, tendons and muscles. These forces are found to be greatly weakened by neoplastic transformation, however, suggesting that malignant invasiveness results from some sort of deflection of cell traction forces from their proper morphogenetic functions, so as to produce uncontrolled invasion. To explain how motile cells create and maintain structures, as well as how their locomotion sometimes becomes perverted into the form of cancerous invasiveness, what seems to be needed is an extension of the concept of homeostasis to apply to the control of geometric relations between cells. This task may not be easy; one obstacle is the widespread belief that asymptotic stability implies the minimization of free energy. Instead, I suggest that stability results from balance of opposing forces within tissues, and that genes control which anatomical shapes will exist by determining the rules by which the relative strengths of these forces vary as functions of shape: to control shape, one must control the way forces vary with shape.
Harris
A K
AK
Department of Biology, University of North Carolina, Chapel Hill 27599-3280.
D000818:Animals; D002465:Cell Movement; D002642:Chick Embryo; D006706:Homeostasis; D009024:Morphogenesis; D051381:Rats