Dynamic supramolecular hydrogels with adaptive biological functionality

  • Yousef Abul-Haija

Student thesis: Doctoral Thesis


Molecular self-assembly coupled with (bio)catalysis underlie dynamic processes in biology and are considered as powerful tools for fabricating adaptive materials. In nature, the extracellular matrix (ECM) - the complex yet dynamic environment surrounding cells, provides cell support and ultimately determines cell fate. Cell behaviour depends on three main ECM properties; (i) its biochemistry presented by the chemical functionality exposed to the cells, (ii) its (nanoscale) topography and (iii) its mechanical properties (i.e. stiffness). The ultimate goal of this research is to develop materials that could mimic the ECM properties and function with minimal complexity by combining self-assembly and biocatalysis. Aromatic peptide amphiphiles and aromatic sugar amphiphiles are particularly interesting building blocks in this context and were mainly utilised in this work. For the development of applications and novel uses for peptide nanostructures, robust routes for their surface functionalization, that ideally do not interfere with their self-assembly properties, are required. Many existing methods rely on covalent functionalization, where building blocks are appended with functional groups, either pre- or post-assembly. In the first part of this thesis, we demonstrate a facile supramolecular approach for the formation of functionalized nanofibers by combining the advantages of biocatalytic self-assembly and surfactant/gelator co-assembly. This is achieved by enzymatically triggered reconfiguration of free flowing micellar aggregates of pre-gelators and functional surfactants to form nanofibers that incorporate and display the surfactants' functionality at the surface. Furthermore, by varying enzyme concentration, the gel stiffness and supramolecular organization of building blocks can be varied. Then, a non-enzymatically triggered peptide-based hydrogelator was co-assembled with different amino acid and simple sugar based surfactant-like functionality. We aimed to study the effect of chemical functionality of co-assembled two-components on the differentiation of adipose stem cells. Different surfactant-based functionalities (simple amino acid and sugar derivatives) were co-assembled with Fmoc-FF, a well-established hydrogelator. The co-assembled structures were characterised by various techniques including FTIR, fluorescence spectroscopy, circular dichroism, zeta potential, TEM and rheology. Depending on the components chemistry, co-assembly mode can be affected by the chemical functionality presented on the surface of the nanofibres. Moreover, the mechanical properties of the formed hydrogels could be tuned by varying the total concentration of the co-assembled components. After that the ability of simple sugar amphiphiles to self-assemble into nanofibers upon enzymatic dephosphorylation was investigated. The self-assembly process can be triggered by alkaline phosphatase (ALP) in solution or in situ by the ALP produced by osteosarcoma cell line, SaOs2. In the former case, self-assembly rate, mechanical properties (stiffness) and the supramolecular organisation could be controlled. In the latter case, assembly and localized gelation occurs mainly on the cell surface. The gelation of the pericellular environment induces a reduction of the SaOs2 metabolic activity at an initial stage (≤7 h) that results in cell death at longer exposure periods (≥24 h). We show that this effect depends on the phosphatase concentration and thus, it is cell-selective with prechondrocytes ATDC5 (that express ~15-20 times lower ALP activity compared to SaOs2) not being affected at concentrations ≤ 1 mM. These results demonstrate that simple carbohydrate derivatives can be used in an anti-osteosarcoma strategy with limited impact on the surrounding healthy cells/tissues. Biological syst
Date of Award14 Jul 2015
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SupervisorRein Ulijn (Supervisor) & Peter Skabara (Supervisor)

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