• Cell groups push, rather than pull, them

    From ScienceDaily@1:317/3 to All on Mon Feb 14 21:30:48 2022
    Cell groups push, rather than pull, themselves into place as organs form
    and cancers spread

    Date:
    February 14, 2022
    Source:
    NYU Langone Health / NYU Grossman School of Medicine
    Summary:
    A new study found in a living embryo that the back ends of moving
    cell groups push the group forward, with implications for how
    organs form and cancer spreads.



    FULL STORY ========================================================================== Cells push and pull on surrounding tissue to move in groups as they form
    organs in an embryo, track down invading bacteria, and as they become
    cancerous and spread.


    ========================================================================== Published online in Nature Cell Biologyon February 14, a new study found
    in a living embryo that the back ends of moving cell groups push the
    group forward.

    This runs contrary to previous findings, where cell groups grown in dishes
    of nutrients (cultures) pulled themselves forward with their front edges.

    Led by researchers from NYU Grossman School of Medicine and the NYU
    Courant Institute of Mathematical Sciences, the study used a new
    technique to measure the forces applied by a cell group as it moved
    along a "road-like" tissue membrane and into place in a developing
    animal. Specifically, the study found for the first time in an animal
    tissue that proteins called integrins on the surfaces of the cells at
    the rear attach in greater numbers to the membrane as they move along,
    and exert more force in one direction, than the cells in the group's
    front. The integrin clusters (focal adhesions) observed in the embryo
    were smaller than those seen in culture studies, and broke down faster.

    Confirmation of such mechanistic details in living tissue have important implications, say the researchers, as many cancers spread in cell groups,
    and may use the newfound "rear engine propulsion." "Our results clarify
    how cell groups that will become organs move into place, and reaffirm that cells behave differently when removed from their natural environments,"
    said senior study author Holger Knaut, PhD, associate professor in the Department of Cell Biology at NYU Langone Health.

    Study Details The study results are based on mechanisms of cell movement established by past studies. For instance, a protein called actin is
    known to form the protein "skeleton" of cells, with actin chains able
    to grow in a certain direction, and apply force that change a cell's
    shape. Integrins, proteins built into outer cell membranes, interact
    both with actin networks, and proteins outside of cells. These and other proteins form a system that a cell uses to briefly attach to and "roll
    along" a basement membrane, a pliable mesh of proteins and sugars. What
    was unknown going into the current study was how tissues in living
    animals apply force in groups to generate this motion.



    ==========================================================================
    The new study examined cell group motion in a zebrafish embryo, a
    major model in the study of development because it shares many cellular mechanisms with human cells, and because zebrafish embryos development externally, such that each stage in development can be directly observed
    using high-powered microscopes. In this way the team tracked the movement
    of the primordium -- a tissue made up of about 140 cells -- as it migrated during development from behind the ear to the tip of the zebrafish tail,
    where it matures into an organ that senses water flow.

    "In the first study of its kind, we combined advanced microscopy with automated, high-throughput computational modeling to measure cellular
    forces in living organisms," says co-corresponding author Daniele Panozzo,
    PhD, an associate professor at the Courant Institute of Mathematical
    Sciences at New York University.

    Using "bleached" dots on the basement membrane to measure shape changes (deformations) on a minute scale, and a new software called embryogram to calculate how far the dots move as the primordium "grips" the membrane,
    the researchers determined how much the cells pulled and pushed on the membrane, "like a tire on pavement." The effect is much like the high
    school physics experiment where students draw two dots on a rubber band,
    and calculate the force applied as they stretch the band by measuring
    the change in distance between the dots.

    With these tools in hand, the team showed that the primordium cells link
    the force-generating actin-myosin network at the back end of the moving
    group through integrin clusters on the side closest to the basement
    membrane. The team theorizes that cells attached to membrane toward the
    back push on the cells in front of them to move the entire group. The researches also gained new insights on an established mechanism where
    cells have surface proteins that let them "sense" and follow a guidance
    cue called a chemokine, from low concentration to high concentration. The
    new study found, however, that cells toward the back end of the primordium sense the chemokine gradient more strongly.

    Interestingly, the study found that the primordium moved in a "continuous breaststroke" by pushing the basement membrane downward, sideways and backwards, much like the arms of a swimmer. The authors do not know
    why this is, but speculate that this is the most efficient way to move
    forward. They note that banana slugs also use the rear edge of the "foot"
    they apply to the ground, suggesting that evolution favors rear engine propulsions because they are most efficient at different size scales.

    The study suggests that group cell movement have the potential to be
    harnessed to stop cancer spread, perhaps by designing treatments that
    block the action of integrins, say the authors. Integrin inhibitors
    have been tested as drugs for cardiovascular and autoimmune disease in
    clinical trials, but their use against cancer spread has been limited
    by the need for a better understanding of the mechanisms.

    Along with Knaut and Panozzo, study authors were Naoya Yamaguchi, Ziyi
    Zhang, and Teseo Schneider from New York University, and Biran Wang
    from Memorial Sloan Kettering Cancer Center. The work was supported
    by National Institutes of Health grant NS102322, NYSTEM fellowship
    C322560GG, by an American Heart Association fellowship 20PRE35180164 ,
    and by National Science Foundation grants 1652515, IIS-1320635 (D.N.), OAC-1835712, OIA-1937043, CHS-1908767, CHS- 1901091, as well as by gifts
    from Adobe Research, nTopology, and Advanced Micro Devices, Inc.

    ========================================================================== Story Source: Materials provided by NYU_Langone_Health_/_NYU_Grossman_School_of_Medicine.

    Note: Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Naoya Yamaguchi, Ziyi Zhang, Teseo Schneider, Biran Wang, Daniele
    Panozzo, Holger Knaut. Rear traction forces drive adherent
    tissue migration in vivo. Nature Cell Biology, 2022; DOI:
    10.1038/s41556-022- 00844-9 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/02/220214111822.htm

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