W. Richard Bowen and Nidal Hilal 4

218 7. MICRO/NANOENgINEERINg ANd AFM FOR CELLULAR SENSINg
or physical in nature, have been reliably produced by various methods.
Many of these structures have emerged from the novel combination of
advances in micro- or nanofabrication, chemistry and biology. Surface
patterning methods offer considerable flexibility in pattern design, ligand
specificity and density, and surface composition to investigate interactions
of cells with chemical variations in the ECM. A vast range of engineered
topographic features, from micro- to nanoscale, have been found to play a
significant regulatory role in cellular proliferation, migration and differentiation.
These studies provide significant insights into mechanistic questions
of how cells are able to sense, integrate and respond to collective
chemical and mechanical signals. In addition, they also demonstrate that
engineered environments can regulate cell functions and fate, and thus
open new opportunities of developing tailored biosubstrates for specific
tissue cell types, although this is still at its early stage.
Optical microscopes and SEM have been essential tools for many of
these studies; however, they are subject to many constraints in exploring
the molecular mechanisms at subcellular or cellular level, which are essential
for the control of the biological pathway. AFM, having been established
as an important tool in development of nanopatterned surfaces,
has provided increased momentum to living system studies. Nanometre
spatial imaging and quantitative measurement of mechanical properties
of functional components of a living cell have been reliably achieved.
Long standing questions in the nanoworld, such as whether it is nanoscale
topographic features or chemical patterns that predominate in inducing
cellular reactions [40], may be answerable. The combination of AFM
with existing optical techniques has already shown itself to be a powerful
tool, and further insights will be gained into in vitro cell differentiation and
disease diagnostics. Together with the engineered environments that can
be employed to guide cell function and fate, it might be possible to move
towards controlling biological pathways in cell culture, and so explore new
medicines and therapies for human health.
There are still many open challenges in cell biology and in physiological
and pathological dysfunctions. The convergence of micro- or nanoengineering,
AFM and interfacial chemistry with cell biology tools might
provide new opportunities to address these challenges. For example, a better
understanding of the complex processes associated with a whole intact
cell interacting with individual molecules when cells are in contact with a
surface will facilitate the diagnostics of arthoroplastic failures and improve
existing implants. A more ambitious approach is to regenerate failed tissue
outside a body; this requires an engineered ECM with the functionalities
that are found in a body. Although there have been intensive efforts in
these fields, researchers are still a long way from recreating an ECM with
similar molecular architecture and functionalities of the ECM found in vivo.