The Role of Sugars for Protein Stabilization
Doktorsavhandling, 2018

The understanding of biomolecular interactions with water and co-solutes can lead to greater knowledge regarding the mechanisms behind biomolecular stabilization. This is highly important for developing technologies aimed to preserve biological materials. Such techniques include cryopreservation of pharmaceuticals or human organ transplants, for example. For these purposes, the disaccharide trehalose has been shown to be an outstanding biomolecular stabilizing agent during cryostorage or storage of desiccated materials.

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.








neutron scattering



neutron diffraction

dielectric spectroscopy

PJ-salen, Origohuset.
Opponent: Salvatore Magazù, University of Messina, Italien


Christoffer Olsson

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

Preserving biological materials is becoming more and more important for a broad range of different fields. Pharmaceutics are becoming increasingly structurally complex and are therefore inherently less stable which increases the need for these to be stabilized by different methods for long-term storage. Furthermore, advances in biotechnology related to, for example, tissue engineering and blood transfusion increases the demand for techniques of storing large complex biological materials. In order to develop such techniques, researchers have taken inspiration from different organisms, such as the tardigrade, which are capable of surviving extreme environments for extended periods of time. It has been found that many of these so-called extremophiles use different types of sugar molecules to survive harsh conditions. Among these sugar molecules, the disaccharide trehalose has been found to have extraordinary protective properties. Therefore, by studying the interaction of trehalose with different biological materials it is possible to learn more about how to improve different preservation techniques, such as cryopreservation or freeze-drying.


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), 2012-01-01 -- 2015-12-31.

Vetenskapsrådet (VR), 2016-01-01 -- 2019-12-31.


Fysikalisk kemi

Biokemi och molekylärbiologi


Den kondenserade materiens fysik


C3SE (Chalmers Centre for Computational Science and Engineering)


Livsvetenskaper och teknik




Doktorsavhandlingar vid Chalmers tekniska högskola. Ny serie: 4489


Chalmers tekniska högskola

PJ-salen, Origohuset.

Opponent: Salvatore Magazù, University of Messina, Italien

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