Thesis

Development of peptoid material for cell growth and differentiation

Creator
Rights statement
Awarding institution
  • University of Strathclyde
Date of award
  • 2022
Thesis identifier
  • T16254
Person Identifier (Local)
  • 201758299
Qualification Level
Qualification Name
Department, School or Faculty
Abstract
  • Development of new systems that mimic the native cellular environment hasemerged as one of the main strategies for tissue engineering and futurebiomedical applications. While nanoparticles (NPs) and nanotubes (NTs)positioned themselves as candidates of high potential in the field, more andmore studies emphasize their size-related cytotoxicity, the difficulty oftranslating them from research laboratories into the clinic, and in conductinglarge-scale synthesis.Peptoids are peptide mimetics. The only difference from natural peptides isthat the side chain is shifted from the backbone alpha carbon on the peptideto the nitrogen atom on the peptoid. This structural difference confers onpeptoids several interesting properties such as biostability, and easy andeconomical synthesis. While the side chain shift deprives the peptoids fromchiral centres and backbone secondary structure hydrogen bonding, theincorporation of specific side chains enables the folding of the peptoid chainsinto organised secondary structures such as nanosheets.This thesis presents the study of two different peptoid systems and theirinteraction with cells, namely peptoid nanosheets and a peptoid hydrogel. Theaim was to create peptoid materials inspired by the mechanisms ofextracellular matrix (ECM)-cell interaction to control stem cell growth anddifferentiation. In the first and major part of the thesis, we focused on themechanical and biochemical properties. We wanted to mimic the mechanicalinteraction of the ECM that is displaying biologically relevant peptide ligandswith cells. This was carried out by developing peptoid nanosheets (PNS) as astiff and functionalizable platform and characterizing their effect on cells.Those PNS combine the following advantages: a structure close to the bilayercell membrane, a peptidic nature and cell size similarity, stiff intrinsicmechanical strength, biocompatibility and the possibility of surfacefunctionalisation with different types of ligands with high degree of control.In the second part, we wanted to capture the dynamic properties of the 3Denvironment provided by the ECM by beginning to develop a peptoid hydrogelthat is capable of changing its mechanical stiffness upon exposure to astimulus.This thesis describes not only the effect of the peptoid systems on MSCs butalso the strategy and steps taken to develop a cell culture system capable ofsustaining the integrity of both cells and PNS, as this is the first time the effectof 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 evadethe drawbacks of conventional nanomaterials used with biological systems.
Advisor / supervisor
  • Lau, K. H. Aaron
Resource Type
Note
  • Previously held under moratorium from 7th June 2022 until 12th May 2023.
DOI

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