Cellular Dyes and Bioactive Peptides - Cell Membrane Interactions and Cellular Uptake
Doktorsavhandling, 2014

Knowledge about mechanisms behind interactions of molecules with biomembranes and cellular uptake is very important for understanding biological processes and for drug design. The work described in this thesis has focused on interactions of cellular dyes and bioactive peptides with cells and the cell membrane. Cellular dyes can be used to investigate processes occurring in the cell since they enhance the contrast of specific intracellular areas or molecules. Here, two types of dyes have been investigated; ruthenium dipyridophenazine complexes and voltage-sensitive dyes. Further, bioactive peptides have gained an increased attention for promising therapeutic applications. In this thesis, the cellular uptake of cell-penetrating peptides, interesting as drug delivery systems, and of the antisecretory peptide, AF-16, is examined. For the development of compounds of both categories, a large challenge is to overcome the poor cellular uptake, which is restricted by the cell membrane, and to understand the mechanisms of interactions with the cell membrane. The results show that ruthenium dipyridophenazine complexes, interesting as cellular dyes because of their low background emission, have tunable affinity for biomembranes and nucleic acids upon slight changes of their lipophilicity and stereochemistry. These complexes enter cells in two different ways, by endocytosis and by a photoactivated uptake mechanism. The voltage-sensitive dyes, which are used for visualization of the membrane potential variation by microscopy, seem to interact with lipid membranes in a dimeric form. For the studied series of arginine- and tryptophan-rich cell-penetrating peptides, the cellular uptake efficiency was found to be sequence specific, both regarding the number and the position of the tryptophan residues. Concerning the therapeutic peptide AF-16, its cellular uptake is mediated by endocytosis, which is enhanced by the presence of cell-surface proteoglycans. The results in this thesis give insights in membrane binding properties and cellular uptake of dyes and bioactive peptides as well as factors influencing these interactions, important knowledge for inspiring in future development of diagnostic and therapeutic molecules.

Membrane Interactions

Spectroscopy

Cell-Penetrating Peptides

Bioactive Peptides

Cell Membrane

Confocal Laser Scanning Microscopy

Cellular Uptake

AF-16

Voltage-Sensitive Dyes

Cell Dyes

Antisecretory Factor

Ruthenium Complexes

Isothermal Titration Calorimetry

Flow-Cytometry

Kollektorn
Opponent: Astrid Gräslund, Biochemistry and Biophysics, Stockolm University, Sweden

Författare

Maria Matson Dzebo

Chalmers, Kemi- och bioteknik, Fysikalisk kemi

Effects of Tryptophan Content and Backbone Spacing on the Uptake Efficiency of Cell-Penetrating Peptides

Biochemistry,; Vol. 51(2012)p. 5531-5539

Artikel i vetenskaplig tidskrift

Enhanced Cellular Uptake of Antisecretory Peptide AF-16 through Proteoglycan Binding

Biochemistry,; Vol. 53(2014)p. 6566-6573

Artikel i vetenskaplig tidskrift

Lipophilic ruthenium complexes with tuned cell membrane affinity and photoactivated uptake

Biophysical Chemistry,; Vol. 149(2010)p. 102-106

Artikel i vetenskaplig tidskrift

Correlation Between Cellular Localization and Binding Preference to RNA, DNA, and Phospholipid Membrane for Luminescent Ruthenium(II) Complexes

Journal of Physical Chemistry B,; Vol. 115(2011)p. 1706-1711

Artikel i vetenskaplig tidskrift

Styrkeområden

Nanovetenskap och nanoteknik

Livsvetenskaper och teknik

Ämneskategorier

Fysikalisk kemi

Biokemi och molekylärbiologi

Biofysik

Fundament

Grundläggande vetenskaper

ISBN

978-91-7597-096-7

Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 3777

Kollektorn

Opponent: Astrid Gräslund, Biochemistry and Biophysics, Stockolm University, Sweden

Mer information

Skapat

2017-10-07