Biomedical Engineering Reference
In-Depth Information
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Young's modulus, E (kPa)
Fig. 7.25. Using AFM to diagnose cancer - nanomechanical measurements of live cells. Left:
optical view of an AFM cantilever probing mixed healthy and tumourous cells. Middle: Young's
modulus of healthy cells. Right: Young's modulus of tumour cells. The cells were differentiated by
immunostaining. The AFM-based nanoindentation results show that the tumour cells are much less
stiff, enabling cell motility in the body. Adapted with permission from [680].
the high-resolution imaging, and also the ability to image not only the cell, but it's
surroundings, studies of the interactions between cells and their substrate are a strong
point of AFM-based cell studies [175, 678]. For example via AFM it's possible to observe
cell responses to nanostructured surfaces, and even to observe the cell-surface interactions
in real time with living cells [664].
Mechanical properties of animal cells are very important for their functions, and thus it
is useful that AFM can measure cellular mechanical properties at the single cell, or sub-
cellular level [668, 679-681]. It is possible to determine differences in stiffness between
different parts of the same cell, typically showing the presence of sub-membrane cell
components. One example of the utility of this is in probing the mechanical differences
between diseased and healthy cells. Recently it was realized that an important factor
leading to tumour invasion and metastasis is a decrease in cell stiffness, leading to
increased ability to spread throughout the body [682]. AFM has been used to prove that
tumour cells collected from patients are considerably less stiff than healthy cells from the
same patients. Further, it appeared that various types of cancer cell, all from different
patients exhibited very similar stiffness values [681]. The AFM-based measurement of
stiffness was proposed as a diagnostic method for forms of cancer that are difficult to
diagnose by traditional methods [680, 681]. In addition to nanoindentation experiments,
force spectroscopy experiments have been widely applied to living mammalian cells,
which are covered in the next section.
7.3.5 Biological force spectroscopy
Intermolecular interactions are the basis of life, and an extremely important part of
biological research, so an enormous range of techniques have been applied to their
study. For the interactions of biological molecules, AFM has some unique advantages. It
is very sensitive, allowing the interactions between single pairs of molecules to be studied
due to force resolution in the 10 pN range [683]. Moreover, it can be very selective. The
control over the
x
,
y
and
z
position of the probe with immobilized molecules means that
unlike most techniques, by AFM-based force spectroscopy, it's possible to control exactly
