Surface switch turns on cell culture
Professor Magnus Berggren and his research group have developed an electronic surface – a surface switch – based on organic electronic materials. It enables the researchers to control both the growth and the differentiation of stem cells.
The group started researching its surface switch about ten years ago. The starting point is the hinged plastic PEDOT, a conjugated polymer consisting of long molecular chains with alternating double and single bonds. This means electric charges can move along the chain – they can even jump between chains. Hence PEDOT is a good conductor of electricity, can conduct ions and is biocompatible. It also thrives together with human cells.
Two electrodes in PEDOT were placed as thin films in a microscope slide and when current was passed through, one side of the glass reduced and the other side oxidised, i.e. one side became hydrophobic and the other hydrophilic. On one side the proteins are oriented in one way and on the other side in a completely different way.
“Kristin Persson, a PhD student in our group, played with this phenomenon for a while. Then we met some colleagues from Karolinska institutet who said that if we can control the wetting then we should also be able to control the growth and differentiation of stem cells,” Prof Berggren explains.
The researchers started trials to culture cells on surfaces of PEDOT, and because they could control the formation of the proteins, they could also control growth. On the reduced side the cells thrived and grew together, while on the oxidised side they slowly died – apoptosis occurred. The results were published in 2009.
A few years ago the research group developed an organic transistor with which one can control and adjust the amount, formation and orientation of proteins along a gradient. Thus it became possible to translate electric signals into chemical gradients, and in turn to control the concentration and extension of the cells.
“We discovered that 0.7 V is a suitable voltage, where the cells thrive especially well on the surface, but we don’t yet know why this voltage gives the best results,” says Prof Berggren.
Then new trials were conducted, aimed at culturing stem cells to get them to differentiate – to develop in different directions. The researchers studied the growth factors that are bound in the protein heparin. It turned out that on the reduced surface the concentration of growth factors was three to five times higher because the heparin could spread out and release growth factors. On the oxidised side however, the growth factors were still firmly bound to the PEDOT electrode. Depending on whether the PEDOT electrode is in its reduced or oxidised state, the stem cells can develop into either muscle cells or astrocyte cells (a type of nerve cell). This result was published in 2011.
The next step was to try to utilise the PEDOT surface switch, and the capacity to change from reduced and bound to oxidised and water soluble, for the culture of skin. Gunnar Kratz, professor at IKE, had problems harvesting cultured tissue, as too many cells were damaged when the culture was removed from the cell culturing surface.
“Our technology works like an electronic glue. We have tested building epithelial cells and when we changed the oxidation state with the help of the surface switch the cells easily released from the surface. It proved to be gentler than the classic chemical methods that were previously used to remove cells and tissue. The cells were more active and fewer were damaged,” Prof Berggren says.
Their work continues, as they refine the methods of controlling and adjusting the growth of cells, in order to differentiate stem cells and release tissue. Hence their research also contributes to Linköping University’s focus on regenerative medicine, i.e. research aimed at recreating damaged organs and tissue where otherwise scar tissue would have formed.
By: Monica Westman Svenselius