Self-Organization of β-Peptide Nucleic Acid Helices for Membrane Scaffolding

by Geralin Höger
Doctoral thesis
Date of Examination:2019-02-14
Date of issue:2019-08-06
Advisor:Prof. Dr. Ulf Diederichsen
Referee:Prof. Dr. Ulf Diederichsen
Referee:Prof. Dr. Claudia Steinem
Persistent Address: http://dx.doi.org/10.53846/goediss-7585

 

 

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Abstract

English

In a vast number of cellular processes interactions between membranes and proteins are essential, resulting in the lipid bilayer being interspersed immensely with proteins. Apart from catalytic or signaling functions, a tremendous amount of proteins is constituted of cytoskeletal components which line the cytoplasmic side of the plasma membrane as a mesh-like network and provide stability and shape of the cell. Numerous studies have been conducted to apprehend this so-called membrane skeleton and its underlying dynamics, however, many aspects remain obscure. Therefore, model systems with reduced complexity and specific interaction sites became a valuable tool to study the influence of peripheral networks on lipid bilayers. In this study, the design, synthesis and investigation of an artificial model system based on β-peptide nucleic acid (β-PNA) helices in order to assess the requirements for an aggregational system on lipid bilayer surfaces is displayed. After optimization of the solid phase peptide synthesis (SPPS) conditions to attain higher synthesis efficiency, different β-PNA systems with and without hydrophobic modifications for membrane attachment were realized and characterized by circular dichroism (CD) spectroscopy. Analyses conducted in solution via fluorescence spectroscopy and CD spectroscopy revealed the potential of β-PNA helices without hydrophobic modifications to form dimers which can be controlled by the number and sequence of the interacting nucleobases as well as by temperature. Furthermore, analyses conducted on membrane surfaces using β-PNA helices with hydrophobic modifications revealed simultaneous β-PNA/β-PNA and β-PNA/membrane interaction.
Keywords: solid phase peptide synthesis (SPPS); membrane scaffolding; membrane-associated protein networks; β-peptide nucleic acids (β-PNA); circular dichroism (CD) spectroscopy; fluorescence resonance energy transfer (FRET); fluorescence spectroscopy; ultraviolet–visible (UV/Vis) spectroscopy
 
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