ATOMIC FORCE MICROSCOPY FOR MEDICINE - Life at the Nanoscale: Atomic Force Microscopy of Live Cells - page 418

showing about a 50-70% accuracy for diagnosing cancer. 7 Despite using
complementary techniques, including histochemical, immunohistochemical
and ultrastructural techniques, to develop better diagnostic protocols, the
ability to detect early-stage tumours, such as those of the breast, prostate,
cervix or colon, has not signiicantly improved in the past 30 years. 7 The
need for developing new technologies to overcome these limitations is thus
evident. Cellular and molecular biomechanics of cancer cells is an exciting
area, which characterizes the rheological properties of cancer cells and relates
the measurable mechanical properties to their molecular basis. Changes
in the rheological properties may provide useful information for cancer
diagnosis and physical evidence to understand therapeutic mechanisms of
various anti-cancer agents. Recent advances in experimental biomechanics
have enabled direct and real-time mechanical probing and manipulation of
single cells and molecules with nano and picoscale resolutions.
Several studies reported on differences in rigidity of cancer cells
from normal cells. 8 Although the detailed physiological mechanisms and
propagation of mechanical properties of normal versus tumour cells are still
being investigated, AFM-based cytological analysis provides an entirely new
technological platform for cancer diagnosis and evaluation by quantitatively
measuring the Young's modulus of cells. 9 Low stiffness of cancer cells may
be caused by a partial loss of actin ilaments and/or microtubules, and
therefore lowers the density of the cellular scaffold. 10 In general, malignant
cells respond either more elastically (softer) or less viscously to the applied
stress since metastatic cells must squeeze to go through the surrounding
tissue matrix when they make their way into the circulatory systems where
they are directed to establish distant settlements. 11
AFM has emerged as an important instrument for the investigation of
mechanical properties associated with live cells. 12 It is considered as a
powerful tool for probing biological samples with sub-nanometre resolution
thus providing tremendous insight regarding the surface features and
cellular nanomechanics, 13 or cellular processes based on the mechanical
properties of living cells. 14 An AFM consists of a cantilever (with tip mounted
to the soft cantilever spring), a sample stage and an optical beam delection
system which consists of a laser diode and a position-sensitive photodiode.
A schematic diagram of an AFM tip interacting with an individual cell is
shown in Fig. 20.3.
Mechanical measurements acquired using AFM rely on measuring the
force as the tip is pushed towards ( Fig. 20.3a ) , indented into ( Fig. 20.3b )
and retracted from the sample or cell surface in this case ( Fig. 20.3c ) . The
cantilever is mounted on the end of a piezoelectric tube scanner which is
used to bring the tip into contact with the surface. The force is measured