From single-molecule sensing to extracellular vesicles in glioma cells under stress
Doktorsavhandling, 2017

This thesis describes the work I conducted in two different areas, namely biomolecular sensing and quantitative cell biology. The work in the former area was focused on the optimization of plasmonic metamaterials for sensing applications, and in the latter on the characterization of extracellular vesicles released by glioblastoma cells under stress conditions. If these two areas appear to be very far apart, it is because they are; however, they are not entirely disconnected. Understanding the biological function of extracellular vesicles depends on the information that can be obtained using bioanalytical sensors, which consequently relates to the information that can be gained from cellular experiments. Attempts were therefore made to review and exploit biophysical approaches that link the two areas, with focus on how detailed insights about the nature of these vesicles relate to their biological function. At its core, this thesis deals with: i) plasmonic biomolecular sensing, discussing noiserelated issues, single-molecule detection and a dual-wavelength method to extract more – and more accurate – information from ensemble measurements of complex macromolecular entities, including extracellular vesicles; ii) an introduction to glioblastomas, cellular models of hypoxic and oxidative stress, the role of extracellular vesicles in cellular communication in cancer, and an exploratory omics approach to understand how the biochemical composition of cells and vesicles changes across different cell lines in response to stress. As an encompassing bridge, a review on the techniques used to characterize extracellular vesicles also acts as an integrating element of this thesis and will help the reader understand different aspects of relevance with respect to how the physical and biological viewpoints intersect. The main findings of the work on biomolecular sensing consist in: i) the clarification of the interplay between inhomogeneous binding probability to a nanosensor (which depends on diffusion/geometry) and the inhomogeneous sensitivity distribution of the nanosensor itself as combined sources of detection uncertainty and ii) a method exploiting dual-wavelength plasmonic sensing to estimate the degree of deformation of adsorbed extracellular vesicles and hence more accurate determination of their mean size and bulk concentration. In the second area we find that iii) the proteome of vesicles mainly depends on cell type of origin and is greatly affected by stress, although in a heterogeneous way, with respect to the cells proteome; on the contrary, iv) the lipid composition of extracellular vesicles is very stable across cell types and stress.

proteome

single molecule sensing

nanoplasmonics

surface plasmon resonance

exosomes

glioblastoma

extracellular vesicles

cellular stress

lipid composition

Kollektorn, MC2
Opponent: Marica Ericson, Göteborgs Universitet

Författare

Virginia Claudio

Chalmers, Fysik, Biologisk fysik

A simple model for the resonance shift of localized plasmons due to dielectric particle adhesion

Optics Express,; Vol. 20(2012)p. 524-533

Artikel i vetenskaplig tidskrift

Single-Particle Plasmon Sensing of Discrete Molecular Events: Binding Position versus Signal Variations for Different Sensor Geometries

Journal of Physical Chemistry C,; Vol. 118(2014)p. 6980-6988

Artikel i vetenskaplig tidskrift

Methods for the physical characterization and quantification of extracellular vesicles in biological samples

Biochimica et Biophysica Acta - General Subjects,; Vol. Epub ahead of print(2017)p. 3164-3179

Artikel i vetenskaplig tidskrift

Virginia Claudio, Ágota C. Tuzesi, Wojciech Michno, Chesia Testa, Prince N. Twum, Jörg Hanrieder, Helena Carén, H. Georg Kuhn - Extracellular vesicles from glioma stem cells show cell-line specific proteomes and mainly heterogeneous response to stress

Ämneskategorier

Cellbiologi

Cell- och molekylärbiologi

Annan fysik

Biofysik

Bioinformatik och systembiologi

Cancer och onkologi

ISBN

978-91-7597-591-7

Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4272

Utgivare

Chalmers tekniska högskola

Kollektorn, MC2

Opponent: Marica Ericson, Göteborgs Universitet

Mer information

Skapat

2017-05-12