New study provides clues to decades-old mystery about cell movement
Game-changing discovery impacts tissue engineering, wound healing, and
cancer research

Date:
July 22, 2021
Source:
University of Minnesota
Summary:
A new study shows that the stiffness of protein fibers in tissues,
like collagen, are a key component in controlling the movement
of cells. The groundbreaking discovery provides the first proof
of a theory from the early 1980s and could have a major impact
on fields that study cell movement from regenerative medicine to
cancer research.



FULL STORY ==========================================================================
A new study, led by University of Minnesota Twin Cities engineering researchers, shows that the stiffness of protein fibers in tissues, like collagen, are a key component in controlling the movement of cells. The groundbreaking discovery provides the first proof of a theory from the
early 1980s and could have a major impact on fields that study cell
movement from regenerative medicine to cancer research.


==========================================================================
The research is published in the Proceedings of the National Academy
of Sciences of the United States of America (PNAS), a peer-reviewed, multidisciplinary, high-impact scientific journal.

Directed cell movement, or what scientists call "cell contact guidance,"
refers to a phenomenon when the orientation of cells is influenced by
the alignment of fibers within soft tissues. Cells have protrusions,
almost like multiple little arms, that move them within the tissue. Cells obviously don't have eyes to sense where they are going, so understanding
the mechanisms for how they align their movement with the fibers is
considered by researchers to be a final frontier in controlling cell
migration.

"It's kind of like if someone dropped you in a swimming pool filled
with water and thousands of skinny ropes aligned along the length of the
pool and told you to swim laps -- and then turned off the lights," said
Robert Tranquillo, the senior researcher on the study and a University
of Minnesota professor in the Department of Biomedical Engineering and
the Department of Chemical Engineering and Materials Science. "You'd
reach out your arms and legs to try to move through the water and figure
out the right direction using the ropes." Cells need to move for many
reasons. They must move to the right places in a developing embryo to
become the right cell types. In wound healing, skin cells need to enter
into blood clots efficiently to convert the wound into a scar.

And research shows that when cancer cells migrate away from solid tumors
to spread throughout the body, they're following tracks of a line of
fibers. In more recent years, researchers have found that contact guidance
is the underlying cellular mechanism by which they can make engineered
tissues for regenerative medicine to regrow, repair, or replace damaged
or diseased cells, organs, or tissues.

"Even though we use cell contact guidance for many processes in my lab
to engineer tissues to mimic heart valves and blood vessels, the signal
that induces the cell movement in an aligned fiber network has been
unclear to us all of these years," said Tranquillo, a Distinguished
McKnight University Professor.

In this new study aimed at understanding contact guidance and improving
tissue engineering, Tranquillo's team partnered with researchers at
the University of California, Irvine and University of California, Los
Angeles to test the mechanical resistance (the stiffness of the fibers)
in two different directions in gels of aligned fibers to see if that was
a major factor in cell movement instead of the porosity of the fibers
or the adhesion (stickiness) of the fibers.

"Using a special set of tools previously unavailable to us, we were
able to test skin cells that we consider a 'work horse' for developing engineered tissues," Tranquillo said. "What we found is that when we cross-linked the fibers (connecting them at intersections) and increased
the difference in the stiffness in the two directions, but kept all the
other factors the same, the cells aligned better. This is evidence that
a directional difference in mechanical resistance of the fiber network influences cell orientation and movement." This is the first time anyone
has been able to prove one major aspect of the contact guidance theory
first proposed by Graham Dunn at King's College in London back in 1982, Tranquillo said.

The next steps are to study the porosity and adhesion of the fibers to
see if they have an impact on cell movement, as well as to study other
cell types.

"This is just the first step to truly understand how cells
move," Tranquillo added. "If we can learn more about how
cells move, it could be a game-changer in many scientific fields." ========================================================================== Story Source: Materials provided by University_of_Minnesota. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Greeshma Thrivikraman, Alicja Jagiełło, Victor K. Lai,
Sandra
L. Johnson, Mark Keating, Alexander Nelson, Billianne Schultz,
Connie M.

Wang, Alex J. Levine, Elliot L. Botvinick, Robert
T. Tranquillo. Cell contact guidance via sensing anisotropy of
network mechanical resistance.

Proceedings of the National Academy of Sciences, 2021; 118 (29):
e2024942118 DOI: 10.1073/pnas.2024942118 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210722142029.htm

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