Biology Reference
In-Depth Information
Again, there was no evidence of a circular transmission of force outwards
and away from the AFM tip. Applied force was converted into a biochemical
signal that resulted in focal adhesion remodelling. Traction force vectors
were produced which were discontinuous and again demonstrated the
transmission of force towards and away from the point of contact on the
cell.
The forces and timescales examined in these studies are similar to those
experienced by cells during typical force-distance curve measurements.
This has important implications in our interpretations of such force curves
as clearly the entire cell can respond rapidly and globally to localized contact
forces. Moreover, the elements that control the cellular response are complex
and appear to be species type dependent. This indicates that care must be
taken in interpreting force curves, not only in which mechanical model
is used to extract parameters of interest, but the molecular mechanism
controlling the observed properties must be understood.
If anything, the work presented here has revealed that much remains
unknown when it comes to understanding how the cell regulates and
controls force transmission in two and three dimensions. With the
developments of high-speed confocal imaging and new luorophores it has
become possible to image more than one element of the cytoarchitecture
at a time and with very high temporal resolution. However, simply imaging
structural responses is not enough. Close collaboration between disciplines
is required to then develop predictive and time-dependent models that can
account for the complexities observed experimentally. Understanding the
biological mechanisms of force transduction and force sensitivity has a wide
range of impacts in many ield from a fundamental understanding of cellular
mechanics to healthcare. It has become clear that stem cell differentiation,
apoptosis, mitosis, myogenesis and many other critical physiological
pathways are intimately linked to the cell's ability to sense and respond to
the mechanics and mechanical forces found in their microenvironment.
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The utility of simultaneous AFM and optical approaches is only now
being realized in full detail, and with future technological advancements
the applications may be limitless. The AFM literally provides us with a
inger at the nanoscale which enables us to apply temporally and spatially
controlled forces to live cells and tissues while imaging their structural and
biochemical responses with the wealth of optical approaches now available.
This approach to studying cell mechanics is still very much in its infancy,
but as the simple examples presented here demonstrate, the wealth of new
science in multiple disciplines (physics, biology, medicine, engineering) will
be very exciting.
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