Development of new systems that mimic the native cellular environment has
emerged as one of the main strategies for tissue engineering and future
biomedical applications. While nanoparticles (NPs) and nanotubes (NTs)
positioned themselves as candidates of high potential in the field, more and
more studies emphasize their size-related cytotoxicity, the difficulty of
translating them from research laboratories into the clinic, and in conducting
Peptoids are peptide mimetics. The only difference from natural peptides is
that the side chain is shifted from the backbone alpha carbon on the peptide
to the nitrogen atom on the peptoid. This structural difference confers on
peptoids several interesting properties such as biostability, and easy and
economical synthesis. While the side chain shift deprives the peptoids from
chiral centres and backbone secondary structure hydrogen bonding, the
incorporation of specific side chains enables the folding of the peptoid chains
into organised secondary structures such as nanosheets.
This thesis presents the study of two different peptoid systems and their
interaction with cells, namely peptoid nanosheets and a peptoid hydrogel. The
aim was to create peptoid materials inspired by the mechanisms of
extracellular matrix (ECM)-cell interaction to control stem cell growth and
differentiation. In the first and major part of the thesis, we focused on the
mechanical and biochemical properties. We wanted to mimic the mechanical
interaction of the ECM that is displaying biologically relevant peptide ligands
with cells. This was carried out by developing peptoid nanosheets (PNS) as a
stiff and functionalizable platform and characterizing their effect on cells.
Those PNS combine the following advantages: a structure close to the bilayer
cell membrane, a peptidic nature and cell size similarity, stiff intrinsic
mechanical strength, biocompatibility and the possibility of surface
functionalisation with different types of ligands with high degree of control.
In the second part, we wanted to capture the dynamic properties of the 3D
environment provided by the ECM by beginning to develop a peptoid hydrogel
that is capable of changing its mechanical stiffness upon exposure to a
This thesis describes not only the effect of the peptoid systems on MSCs but
also the strategy and steps taken to develop a cell culture system capable of
sustaining the integrity of both cells and PNS, as this is the first time the effect
of peptoid systems on cells was studied.
To summarise, peptoids are biostable, biocompatible and easy to synthesize,
flexible to functionalise for developing biomimetics in the nano/micro scale.
They have the potential to harness its advantages and at the same time evade
the drawbacks of conventional nanomaterials used with biological systems.
|Date of Award
|13 Jan 2022
- University Of Strathclyde
|University of Strathclyde
|K. H. Aaron Lau (Supervisor) & Duncan Graham (Supervisor)