Scientists at UC San Diego have discovered how cells of higher organisms change the speed at which they move, a basic biological discovery that may help researchers devise ways to prevent cancer cells from spreading throughout the body.
The discovery reported by the UCSD scientists in Proceedings of the National Academy of Sciences (PNAS) and published Aug. 3 on the journal's Web site describes forces and energy exerted by the cells as they traveled across an elastic substrate. In videos recorded as the cells moved, each looked like an irregularly shaped water balloon attached firmly on two sticky sections while periodically protruding in the forward direction and withdrawing from the trailing end.
In humans and other mammals, cell motility is essential for many physiological processes such as tissue renewal and the function of the immune system. Cell motility also is an essential part of embryonic development as fetal cells undergo an orchestrated migration to form functioning tissues and organs. Poorly regulated cell motility during embryonic development may result in some neurological diseases and birth defects such as cleft palate of the mouth. UCSD's new findings may eventually be used to better understand and possibly treat such conditions and suggest possible new cancer treatments aimed at inhibiting the metastatic spreading of some cancer tumors.
Cells of all higher, or eukaryotic, species move in response to external stimuli. This movement is made possible by a series of inter-related biochemical reactions, some of which remodel the internal skeleton and others that add and remove adhesion points at strategic positions on the outer membrane. Regardless of their size or shape, cells use what cell biologists call the cell motility cycle to take one step per cycle: first, the cell extends its leading margin over the substratum forming a pseudopod or foot-like extension; secondly, the tip of the pseudopod develops an adhesion point that attaches to the substratum; next, the cell uses the new point of anchorage to contract; and finally, the trailing adhesion point detaches and the rear part of the cell retracts forward. The process repeats every 1 to 4 minutes in Dictyostelium cells, but the period of the cycle and the length of each step can be shorter or longer in other types of eukaryotic cells.
The scientists discovered that the crawling speed of Dictyostelium is not controlled by the sticking strength of the adhesion points, but rather by the frequency of the cell's motility cycle or how often they take a new step.
For the first time, weve been able to make precise measurements of the repetitive nature of the forces and strain energies exerted by cells, and this has allowed us to better characterize the mechanics of the cell motility cycle, said Juan C. Lasheras, a co-author of the study and a professor of mechanical and aerospace engineering at UCSD's Jacobs School of Engineering.
A cell can assume a variety of shapes due to its internal cytoskeleton, a network of crisscrossed protein fibers that forms an internal skeleton in a cell. The cytoskeleton is also involved in cell motility through its attachments to discrete adhesion regions on the cell membrane. As the cell moves, individual fibers can elongate at one end and shorten at the other.