In this thesis chemical approaches inspired by the extracellular environment are explored. ‘We aim to fabricate cell-instructive biointerfaces,’ says Gulistan Koçer. ‘Light-responsive liquid crystal polymer networks (LCNs) and supported lipid bilayers (SLBs) are presented and discussed, with an emphasis on investigating stem cell behaviour.’
Also endothelial cells (forming layers within blood-vessels) were investigated. ‘Our research is fundamental in nature,’ Gulistan says. ‘By focussing on these kinds of cells, our research becomes clinically relevant. Enhancing responsiveness and functionalization may contribute to various strategies on tissue repair and drugs delivery, as well as the implantation of functionalized stents.’
Working within the Molecular Nanofabrication group (MESA+) and the Bio-inspired Molecular Engineering group (MIRA), a multidisciplinary approach is a given, Gulistan explains. ‘We used chemical strategies in this dynamic environment of human cell interfaces and biomaterial surfaces. Biology, chemistry and material science were equally involved. This approach contributes to worldwide research on this research field in a distinctive way, utilizing the design freedom to the full.’
Exploring and designing new cell-instructive bio-interfaces, has recently been an important focus in biomaterials development for regenerative medicine applications. In this line, progressive developments in materials chemistry, as well as introduction of non-covalent chemistries and stimuli-responsive elements in biomaterials design, have opened up tremendous opportunities.
‘We take highly biomimetic cell-instructive biointerfaces as an inspiration,’ says Gulistan Koçer. ‘With dynamic regulation of physical, chemical and mechanical cues, desired cell and tissue responses can be guided in novel ways.’
It was shown that supported lipid bilayers (SLBs) can be exploited as a cell-instructive platform, in order to gain control over ligand density, mobility, functionalization routes, composition (i.e. type of the peptide ligand), as well as peptide-SLB interactions.
‘Using combinations of these, as a kind of tool box, human mesenchymal stem cell (hMSC) behaviour can be tuned,’ says Gulistan. ‘I conclude that in the near future, research steps can be taken to employ SLBs as cell-instructive interfaces on biomaterials.’
In another main theme within this research, lipid insertion was involved, using alkyl tail or cholesterol modified (lipidated) tripeptide Arg-Gly-Asp (RGD) ligands as functionalization route. ‘We identified the length of the alkyl tail to potentially control hMSC adhesion,’ Gulistan reports.
She was happy to collaborate with PhD colleagues and master students, with a vast expertise in chemistry and biology. ‘In that way I was able to exploit more complicated peptides, to investigate cell-surface interactions,’ Gulistan says. ‘For example, we used a dye-conjugated lipid-modified RGD ligand, which we could monitor very well. We demonstrated the dynamics of the peptide further, and the propensity of hMSCs to take up the peptide.’
Gulistan enjoyed the experimental angle of approach in her PhD work. ‘I like working in the lab, using my hands, designing and building clever experiments. In this PhD I also learnt a lot on synthesizing biofunctional peptides, as well as surface preparation and characterization. It is very informative to perform all research steps from scratch.’
As the PhD project progressed, Gulistan felt more confident in teaching students and collaborating with them on an equal footing. ‘I started to appreciate their entrepreneurial way of handling the problems they encounter,’ she says. ‘At first I was too eager to monitor them all the way through. When students are good and motivated, I found they mature in a quick way and develop as a learning partner. They had a good influence on me in many respects.’
These positive experiences has helped Gulistan to pursue a career in academics further. ‘Besides research, I like teaching too,’ she says. ‘I am now applying for a post-doc position, preferably working on a topic involving dynamic biomaterials research. Here I can use the multidisciplinary approach which I love. Also my experimental skills will be of use, varying from using confocal microscopy, and other imaging techniques, to high throughput screening methods. Further, I learnt to ask advice and collaborate with colleagues when other expertise and facilities are needed.’