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Studying the impact of physical forces on cancer cells
Determining how cancer cells
respond to physical forces in
their cellular environment could
improve cancer treatment,
according to two UC researchers.
Professor Maan Alkaisi and Dr Volker Nock
(Electrical and Computer Engineering) have
been investigating how physical forces in the
micro-nano environment of the body influence
how cells develop, spread and interact, in order
to understand ways cancer treatment could be
enhanced.
“Cancers are more susceptible to metastasise
and spread depending on the stiffness of tissue.
It becomes almost an engineering problem
if you can determine what forces cancer cells
experience in the body,” Nock says.
“We are trying to determine if there are ways
of treating cancer from a different perspective,
not from a mutation-based perspective. There
seems to be a connection between mechanical
stiffness and cancer development and, if we
can determine that and how that affects the
biochemistry of the cells, then there’s potential
to develop drugs that will help.”
Alkaisi and Nock, who have collaborated with
Christchurch Hospital and researchers at
Toulouse University in France, have developed
cutting-edge “bioimprint” technology to find
out how physical forces in the micro-nano
environment influence cell behaviour.
“Physical forces range from nano to microNewtons, so they are extremely small forces that
we are talking about,” Alkaisi says.
24 University of Canterbury
He says bioimprint technology enables
researchers to mimic how cells react by
recreating imitation cells in polymeric material
with features of a similar size and shape to that
of a cell’s morphology.
“We can essentially replicate the micro-nano
environment of the cell by replicating the
cell itself in some polymer, which we use as
a platform to culture cells and see how cells
react to an environment that mimics the shape,
topography and dimensions of an actual cell. We
can do this in a variety of environments, both
positive and negative, for the cell to grow and
interact,” Alkaisi says.
“We have results that show that forces do
influence the morphology, including the shape
or even genetic expression. What the cell secretes
is also different on different topographies, which
means the cell membrane can interact within
an environment and produce different types of
protein to deal with different situations.”
Nock previously worked with a microscopic
worm, C. elegans, to see how the environment
the worm moves in influences forces exerted by
it during locomotion.
“We used a worm which is an excellent model
for all sorts of diseases. We designed devices
with arrays of miniature sensor pillars in which
we could track its movement and every time
it touches a pillar we can measure the force it
exerts by recording the deflection of the pillar.
“We can apply this to cancer cells. We have the
system and we know it works; it is just a matter
of making it smaller for individual cells. There are
some interesting engineering challenges around
the system but, in principle, we know it works,”
Nock says.
Alkaisi says bioimprint technology allows
researchers to determine the difference in the
role of the micro-nano environment and that of
surface chemistry.
“This is probably one of the best technologies to
isolate these two factors. We have a topography
that exactly mimics the environment so we
can isolate the chemical from the physical
influences,” he says.
Alkaisi and Nock, whose research has been
supported by the Marsden Fund, want to apply
their discoveries to measure the forces cancer
cells exert on the micro-nano environment, what
size the forces are, how cancer cells grow and
interact with their environment where tissue is
both soft and hard.
“First, we will measure the forces that cancer
cells exert on the environment and what the size
of those forces are,” Alkaisi says.
“We will look at 3D clusters of cancer cells —
spheroids — growing and see how they push
the surrounding environment under different
conditions. We are going to use the set of pillars
developed by Volker and measure the deflection
of these pillars. From these deflections we can
extract the mechanical and physical forces the
cancer is applying.”
Alkaisi says the ultimate goal will then be to
discover how to apply external forces on the
cancer cells and look at any changes in genetic
expression and changes in growth rate, spread
or behaviour.
“There is an argument in the scientific
community that triggered this research which
proposes that by applying certain forces, cancer
cells can be reverted back to normal cells, which,
if that could be achieved, would be pretty
amazing,” Alkaisi says.
“What we want to do is to build a model whereby
we characterise, exactly, the magnitude and
nature of the forces required to induce changes
and possibly reverse cancer growth.”
Alkaisi says they hope to focus on ovarian cancer,
ultimately using live cancer cells from patients,
because it prefers soft tissue whereas breast
cancer prefers stiffer tissue.
“There is certainly a response to the
environment; this might explain why certain
parts of the body are more vulnerable to cancer
than others. I want to discover what is missing
in cancer treatment. Once we know what impact
mechanical forces could have on cancer cells
then that might give us an idea for developing
better, more effective treatment,” Alkaisi says.
“Medical doctors cannot create devices on such
a small scale to measure forces and detect these
changes so we are hoping this is an area we can
help in.”
Research supported by:
• Marsden Fund
By Renee Jones
(From left) Professor Maan Alkaisi and Dr Volker Nock
Research Report 2014
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