Development of peptoid material for cell growth and differentiation

  • Marwa El Yaagoubi

Student thesis: Doctoral Thesis

Abstract

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 large-scale synthesis. 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 stimulus. 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 Award13 Jan 2022
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde
SupervisorK. H. Aaron Lau (Supervisor) & Duncan Graham (Supervisor)

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