W. Richard Bowen and Nidal Hilal 4
W. Richard Bowen and Nidal Hilal 4
W. Richard Bowen and Nidal Hilal 4
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Au nanoparticles with a cyclic RGD-thiol, nanoisl<strong>and</strong>s of RGD-lig<strong>and</strong>s<br />
are created. This novel method has enabled a series of studies, demonstrating<br />
that cells can detect surface variations at the size of a typical protein<br />
complex (�100 nm) <strong>and</strong> are affected dramatically by small variations<br />
in lig<strong>and</strong>–cluster spacing (e.g. 58 <strong>and</strong> 73 nm) [39].<br />
Although nanopatterning of adhesive molecules is ultimately valuable<br />
to reveal molecular mechanisms underlying cellular processes, the<br />
reliability of the information obtained depends on the accuracy of the<br />
characterisation measurements at the nanoscale. In this context, it should<br />
be noted that topographic features as small as 10 nm can exert dramatic<br />
effects on a cell (more details in the next section). This type of observation<br />
is particularly important for protein nanopatterning studies based on the<br />
assembly of particle templates, as discussed in Spatz’s work.<br />
7.2.2 nanotopography<br />
7.2 ENgINEERINg THE ECM FOR PRObINg CELL SENSINg 205<br />
In contrast to the use of micro- <strong>and</strong> nanoscale patterns of (bio)chemical<br />
motifs described earlier, cell behaviour has also been extensively studied<br />
on patterns of micro- <strong>and</strong> nanoscale topographic features [40].<br />
Motivation for many of these studies comes from the observation that<br />
although the physical form of the ECM appears as a r<strong>and</strong>om meshwork,<br />
in fact, it contains enormously detailed nano- <strong>and</strong> microscale structures.<br />
For instance, a corrugation with a period of 68 nm has been recently<br />
observed on collagen fibres [41]. When looked at on the small scale, the<br />
ECM possesses nanopores, micro- <strong>and</strong> nanofibres, <strong>and</strong> peaks <strong>and</strong> depressions.<br />
Since the middle of the twentieth century, it has been increasingly<br />
recognised that cells react to microtopography. Early evidence has shown<br />
that cells adhere, align <strong>and</strong> move along fibres in the range of 30–100 �m<br />
[42–44]. In recent decades, the advance in micro- <strong>and</strong> nanofabrication has<br />
allowed intense investigations in this area <strong>and</strong> greatly push forward our<br />
underst<strong>and</strong>ing.<br />
Since the early 1960s, Curtis <strong>and</strong> his colleagues have studied the reaction<br />
of a number of cell types with various microtopographic structures<br />
[40, 45]. Microgrooves with a wide combination of widths <strong>and</strong> depths<br />
have been studied, <strong>and</strong> it was found that cells react to both depth <strong>and</strong><br />
width. In general, on deep <strong>and</strong> narrow grooves, cells tend to bridge<br />
between grooves, whilst on shallow grooves, they often follow the surface,<br />
although detailed reactions are cell type dependent [46]. Substantial<br />
evidence has been obtained, showing that adhesion or interaction with<br />
microscale topographic structures induces changes in cell cytoskeletal<br />
organisation, apoptosis (programmed cell death), macrophase activation<br />
(causing inflammatory reactions) <strong>and</strong> gene expression [47, 48]. The<br />
observed phenomena clearly demonstrated that microtopography influences<br />
cell development, <strong>and</strong> thus triggered researchers to pose questions