How molecular muscles help cells divide

Time-lapse videos and computer simulations provide the first concrete molecular explanation of how a cell flexes tiny muscle-like structures to pinch itself into two daughter cells at the end of each cell division, according to a report in Science Express.

Cell biologists at Yale and physicists at Columbia teamed up to model and then observe the way a cell assembles the “contractile ring,” the short-lived force-producing structure that physically divides cells and is always located precisely between the two daughter cell nuclei.

“This contractile ring is thought to operate like an old-fashioned purse string,” said senior author Thomas D. Pollard, Sterling Professor and Chair of the Department of Molecular, Cellular & Developmental Biology at Yale. “It constricts the cell membrane into a cleavage furrow that eventually pinches the cell in two.”

Living cells divide into two daughter cells to reproduce themselves. In one-celled organisms like yeast, each cell division yields a new creature. In humans and other multicellular species, cell division creates an adult from an embryo. In fully developed adults, it provides necessary replacements for cells that are continuously dying in the course of natural wear and tear.

Scientists have long studied aspects of how cells actually make this division — the structure of the cellular machinery, how it assembles and how the machine works. Since the 1970s, it has been known that the contractile ring is made up of muscle-like actin and myosin — contractile proteins that are involved a process in some ways similar to the muscle contraction used to move arms or legs. However, there was no plausible mechanism to explain how it worked.

“We found that fission yeast cells assemble their contractile ring using a ‘search, capture, pull and release’ mechanism,” said Pollard. “This is important because it shows for the first time how the contractile machinery assembles and how all the pieces get to the right place to get the job done.”

Time-lapse imaging and computer modeling demonstrated that cells undergoing mitosis set up small clusters of proteins, or nodes, on the inside of the cell membrane around the equator of the cell. Proteins in these nodes begin to put out a small number of filaments composed of the protein actin. The filaments grow in random directions until they encounter another node, where myosin motors in the contacted node pull on the actin filament, bringing the two nodes together.

However, the researchers found that each connection is broken in about 20 seconds. Releasing the connections and initiating subsequent rounds of “search and capture” appears essential to the assembly process, say the scientists. The assembly involves many episodes of attractions between pairs of nodes proceeding in parallel. Eventually the nodes form into a condensed contractile ring around the equator, ready to pinch the mother into two daughters at a later stage.

“A novel and important aspect of this work was that we used computer simulations at every step to test what is feasible physically and to guide our experiments,” said author Ben O’Shaughnessy, professor of chemical engineering at Columbia. “The simulations show that cells use reaction rates that are nearly ideal to make this mechanism work on the time scale of the events in the cells.”

“Future work will involve testing the concepts learned from fission yeast in other cells to learn if the mechanism is universal,” said Pollard. “Since other cells, including human cells, depend on similar proteins for cytokinesis [cell division], it is entirely possible that they use the same strategy.”

Source: Yale University

Related stories:

Cell division study resolves 50-year-old-debate, may aid cancer research
A new study at Oregon State University has finally resolved a controversy that cellular biologists have been arguing over for nearly 50 years, with findings that may aid research on everything from birth defects and genetic diseases to the most classic "cell division" issue of them all – cancer.
Normalizing tumor vessels to improve cancer therapy
Chemotherapy drugs often never reach the tumors they're intended to treat, and radiation therapy is not always effective, because the blood vessels feeding the tumors are abnormal—"leaky and twisty" in the words of the late Judah Folkman, MD, founder of the Vascular Biology program at Children's Hospital Boston.
Dense tissue promotes aggressive cancers
New research may explain why breast cancer tends to be more aggressive in women with denser breast tissue. Breast cancer cells grown in dense, rigid surroundings step up their invasive activities, Vanderbilt-Ingram Cancer Center investigators report in the Sept. 9 issue of Current Biology.

Purified stem cells restore muscle in mice with muscular dystrophy
By injecting purified stem cells isolated from adult skeletal muscle, researchers have shown they can restore healthy muscle and improve muscle function in mice with a form of muscular dystrophy. Those muscle-building stem cells were derived from a larger pool of so-called satellite cells that normally associate with mature muscle fibers and play a role in muscle growth and repair.
Saving teeth by using periodontal ligament regeneration
Teeth may fall out as a result of inflammation and subsequent destruction of the tissues supporting the teeth. Dutch researcher Agnes Berendsen has investigated a possible solution to this problem. At the Academic Centre for Dentistry Amsterdam (ACTA), she has studied the regeneration of the periodontal ligament by use of tissue engineering. The 3D in vitro model she has developed appears to be promising for regenerating periodontal ligament and may also prove valuable for restoring tendons and ligaments elsewhere in the body.
Stem cells from hair follicles may help 'grow' new blood vessels
For a rich source of stem cells to be engineered into new blood vessels or skin tissue, clinicians may one day look no further than the hair on their patients’ heads, according to new research published earlier this month by University at Buffalo engineers.
Researchers find new way to block destructive rush of immune cells
Researchers have found a way to selectively block the ability of white blood cells to “crawl” toward the sites of injury and infection when such mobility drives disease, according to a study published today in The Journal of Experimental Medicine. The results suggest a new treatment approach for autoimmune diseases like rheumatoid arthritis, lupus and multiple sclerosis, and for conditions made worse by misplaced inflammation, like atherosclerosis, stroke and transplant rejection, researchers said.
Scientists Discover How Cells Build a 'Machine' for Cell Division
Using time-lapse photography and computer modeling, a team of researchers from Columbia, Yale and Lehigh Universities has explained a mystery surrounding the assembly of a cellular structure responsible for cell division, the vital process which enables living creatures to develop from embryo to adult.

News discussion:

General Science news