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Peptide-assisted cancer cell migration along engineered surfaces

Tondo, Rodolfo 2019. Peptide-assisted cancer cell migration along engineered surfaces. PhD Thesis, Cardiff University.
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Abstract

Cell migration is a key process in human biology and the understanding of its complex mechanisms has a crucial importance in biomaterials,[1] engineering, medicine,[2] cell biology and immunology. This important feature is predominant in biochemical processes such as tissue regeneration, cancer metastasis and embryogenesis. Cells can detect chemical and physical gradients both on surface and in solution and respond to them with oriented movement therefore controlling such processes could potentially result in major advances in cancer metastasis treatment and many other cell migrationrelated diseases. It has been described that specific peptide sequences such as Ile- Gly-Asp (IGD, see Fig. 0-1) and Gly-Arg-Gly-Asp (GRGD) interact with the extracellular matrix (ECM), in particular with Fibronectin protein domains inducing adhesion and migratory behaviour on model cells (MDA-MB-231 metastatic breast cancer cells).[3] Such peptides can be tethered onto Au surfaces by means of self-assembled monolayers (SAMs). It is widely known that alkanethiols on Au surfaces form wellordered and stable SAMs, which represent nowadays the most used model substrate for studying cell behaviour.[4] Recent studies performed in our group proved that IGDbearing peptides induce adhesion and then migratory behaviour on metastatic breast cancer cells.[5,6] The goal of this research project is to use such tuneable scaffolds to mimic the extracellular environment, being able to induce and control cell migration towards an anisotropic surface, for a reversible migration movement. Figure 0-1 – Molecular structures of thiolated peptides bearing the motogenic motif IGDQ (IsoLeu-Gly-Asp-Gln; respecting the biological readability of the sequence) and respective nitrobenzyl photolabile linkers. Two different IGD-bearing peptides will be used to pattern Au surface with two concentration gradients in the opposite direction. A photolabile protecting group will be employed in both peptides. The first peptide will induce the first migration and light irradiation at a specific wavelength will remove the protecting group with its motogenic sequence, therefore exposing the opposite gradient towards the surface, for the second migration to occur.

Item Type: Thesis (PhD)
Date Type: Completion
Status: Unpublished
Schools: Chemistry
Date of First Compliant Deposit: 21 April 2020
Last Modified: 21 Apr 2020 15:38
URI: http://orca.cf.ac.uk/id/eprint/131137

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