For scaffold and
imaging applications, nanomaterials such as graphene
and its derivatives have been widely used. Graphitic carbon nitride
(g-C
3
N
4
) is among one such derivative of graphenes,
which draws strong consideration due to its physicochemical properties
and photocatalytic activity. To use g-C
3
N
4
for
biological applications, such as molecular imaging or drug delivery,
it must interact with the epithelium, cross the epithelial barrier,
and then come in contact with the extracellular matrix of the fibroblast
cells. Thus, it becomes essential to understand its molecular mechanism
of action. Hence, in this study, to understand the molecular reprogramming
associated with g-C
3
N
4
, global gene expression
using DNA microarrays and proteomics using tandem mass tag (TMT) labeling
and mass spectrometry were performed in epithelial and fibroblast
cells, respectively. Our results showed that g-C
3
N
4
can cross the epithelial barrier by regulating the adherens
junction proteins. Further, using g-C
3
N
4
–PDMS
scaffolds as a mimic of the extracellular matrix for fibroblast cells,
the common signaling pathways were identified between the epithelium
and fibroblast cells. These pathways include Wnt signaling, integrin
signaling, TGF-β signaling, cadherin signaling, oxidative stress
response, ubiquitin proteasome pathway, and EGF receptor signaling
pathways. These altered signature pathways identified could play a
prominent role in g-C
3
N
4
-mediated cellular interactions
in both epithelial and fibroblast cells. Additionally, β catenin,
EGFR, and MAP2K2 protein–protein interaction networks could
play a prominent role in fibroblast cell proliferation. The findings
could further our knowledge on g-C
3
N
4
-mediated
alterations in cellular molecular signatures, enabling the potential
use of these materials for biological applications such as molecular
imaging and drug delivery.