Abstract:
|
We present a click chemistry-
based molecular toolkit for the bio-
functionalization of materials to selec-
tively control integrin-mediated cell ad-
hesion. To this end,
a
5
b
1-selective
RGD peptidomimetics were covalently
immobilized on Ti-based materials, and
the capacity to promote the selective
binding of
a
5
b
1 was evaluated using a
solid-phase integrin binding assay. This
functionalization strategy yielded surfa-
ces with a nine-fold increased affinity
for
a
5
b
1, in comparison to control
samples, and total selectivity against
the binding of the closely related integ-
rin
a
v
b
3. Moreover, our methodology
allowed the screening of several phos-
phonic acid containing anchoring units
to find the best spacer–anchor moiety
required for establishing an efficient
binding to titanium and to promote se-
lective integrin binding. The integrin
subtype specificity of these biofunc-
tionalized surfaces was further exam-
ined in vitro by inducing selective ad-
hesion of genetically modified fibro-
blasts, which express exclusively the
a
5
b
1 integrin. The versatility of our
molecular toolkit was proven by shift-
ing the cellular specificity of the mate-
rials from
a
5
b
1- to
a
v
b
3-expressing fi-
broblasts by using an
a
v
b
3-selective
peptidomimetic as coating molecule.
The results shown here represent the
first functionalization of Ti-based mate-
rials with
a
5
b
1- or
a
v
b
3-selective pep-
tidomimetics that allow an unprece-
dented control to discriminate between
a
5
b
1- and
a
v
b
3-mediated adhesions.
The role of these two integrins in dif-
ferent biological events is still a matter
of debate and is frequently discussed in
literature. Thus, such bioactive titanium
surfaces will be of great relevance for
the study of integrin-mediated cell ad-
hesion and the development of new bi-
omaterials targeting specific cell types |