The Role of Sugars for Protein Stabilization
In this thesis, the questions regarding the stabilizing role of trehalose is addressed from several different angles. Structural properties of trehalose in water are studied and are compared to those of a similar sugar molecule, namely sucrose. From these studies it was concluded that there were surprisingly small differences between the interactions of trehalose or sucrose with water. The thermodynamic properties of trehalose--water--protein systems were investigated using DSC, where it was indirectly found that the protein hydration shell was not substituted by trehalose, and that the protein stability did not necessarily couple to the glass transition temperature of the trehalose--protein--water-matrix. The structure and dynamics of such a ternary trehalose--water--protein system was also investigated using neutron diffraction combined with EPSR, and QENS combined with an MD simulation. In these studies, it was primarily found that the trehalose molecules were preferentially excluded from the protein surface, and that the local motions of the protein residues were slowed down via a reduction in the motion of the water molecules at the protein surface. Furthermore, the temperature dependences of relaxation dynamics in this system were measured using dielectric spectroscopy. This study showed that the presence of protein hinder certain local trehalose motions, and that the relatively slow dynamics of the trehalose solvent governs the conformational motions of the protein.
The presented results elucidates some fundamental properties of how proteins and trehalose behave and interact, which may benefit the development of new biomolecular protective co-solutes.
Chalmers, Fysik, Biologisk fysik
Olsson, C., Garcia-Sakai, V., Genheden, S., Swenson, J., Mechanism of Trehalose Induced Protein Stabilization from Quasielastic Neutron Scattering and Molecular Dynamics Simulations
Olsson, C., Swenson, J., Structural comparison between sucrose and trehalose in aqueous solution
Olsson, C., Swenson, J., Structural Role of Trehalose for Protein Stabilization and Inhibiting Protein Aggregation from Neutron Diffraction
Olsson, C., Zangana, R., Swenson, J., Dielectric spectroscopy study of proteins embedded in trehalose and water
In this thesis, I investigate how proteins and their environments are affected by the presence of trehalose. In order to investigate this, I have mainly used different types of neutron scattering techniques in combination with molecular simulations, thermodynamic measurements, and dielectric spectroscopy methods.
First, the molecular structure of a mixture of trehalose and water is investigated and compared to a similar system containing another common protective sugar molecule, namely sucrose. The results from these studies indicate that both these sugars exhibit a surprisingly similar structure. Secondly, the molecular structure and dynamics of protein, trehalose, and water-mixtures at different compositions are investigated. From those studies it is shown that the protein molecules prefer to interact with water, thus partially excluding the trehalose molecules from interacting directly with the protein surfaces. It is also shown that the trehalose molecules help to prevent different protein molecules from coming into contact with each other, and that the motions of the protein are slowed down due to a coupling to the trehalose molecules via the water layer at the protein surface.
It is my hope that the presented results will benefit in the pursuit of understanding how trehalose function as a biological stabilizer and may thus help guide future development of improved biomolecular perseveration techniques.
Struktur och dynamik i mjuka och biologiska material. I & II
Vetenskapsrådet (VR), 2016-01-01 -- 2019-12-31.
Vetenskapsrådet (VR), 2012-01-01 -- 2015-12-31.
Biokemi och molekylärbiologi
Den kondenserade materiens fysik
C3SE (Chalmers Centre for Computational Science and Engineering)
Livsvetenskaper och teknik (2010-2018)
Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4489
Opponent: Salvatore Magazù, University of Messina, Italien