FP6Individual fellowship2004–2006

CELLNAC · Modulation of osteoblast function by bioactive RGD-peptides arranged in nanotemplates

FP6 — Marie Curie Actions (Human Resources and Mobility)

Duration
2004-04-01 → 2006-03-31
EU contribution
€160,466
Participants
1
Scheme
EIF

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Results in brief

Final Activity Report Summary - CELLNAC (Modulation of osteoblast function by bioactive RGD-peptides arranged in nanotemplates)

Integrin-mediated adhesion is regulated by multiple features of the adhesive surface, including its chemical composition, topography, and physical properties. In this study we investigated integrin lateral clustering, as a mechanism to control integrin functions, by characterising the effect of nanoscale variations in the spacing between adhesive RGD ligands on cell spreading, migration, and focal adhesion dynamics. For this purpose, we used nanopatterned surfaces, containing RGD-biofunctionalised gold dots, surrounded by passivated gaps. By varying the spacing between the dots, we modulated the clustering of the associated integrins. We show that cell-surface attachment is not sensitive to pattern density, whereas the formation of stable focal adhesions and persistent spreading is. Thus cells plated on a 108-nm-spaced pattern exhibit delayed spreading with repeated protrusion-retraction cycles compared to cells growing on a 58-nm pattern. Cell motility on these surfaces is erratic and nonpersistent, leaving thin membrane tethers bound to the RGD pattern. Dynamic molecular profiling indicated that the adhesion sites formed with the 108-nm pattern undergo rapid turnover and contain reduced levels of zyxin. These findings indicate that a critical RGD density is essential for the establishment of mature and stable integrin adhesions, which, in turn, induce efficient cell spreading and formation of focal adhesions.

Data: CORDIS, © European Union

Project objective

The development of new methodologies in the field of material science and nanotechnology represents a useful tool to further explore and modify biomaterial design. Biocompatiblity is dependent on material-related factors, such as topography and surface chemistry, as well as cell adhesion and function. The focus of this multidisciplinary work is the creation of a system, which permits the study of bone cells adhesion and the regulation of their cellular activities. We propose to use novel chemical techniques to mimic the extracellular environment with bioactive peptides arranged into a rigid well-defined nano-template. We reason that these peptides should control cell attachment and activate integrin-dependent intracellular signaling pathways for bone cell proliferation, differentiation and death by apoptosis. The fellow will gain experience in material science, biophysical chemistry, biophysics, cell biology, and clinical research. The scientific and educational activity will be also embedded in a high quality research and education environment established at the Heidelberg University. Because of her past research experience, the candidate fits excellently to the named project where multidisciplinary skills and knowledge are needed. She will combine her abilities with the abilities of the group of Biophysical Chemistry at the University of Heidelberg, whose main focus is the control of cell adhesion by biophysics and nanotechnology. Until the end of the Marie Curie Fellowship in 2005 she will have the chance to gain enough qualifications to become an associated faculty member in an European Institute or University. The European Community is investing into a young researcher, which will have great potential to connect European research activities in future years. Thus, her will for worldwide mobility is enhancing her own scientific excellence which than will be carried forward to other young scientists and research institutions in Europe.

Original text from CORDIS.

Participants

  • UNIVERSITY OF HEIDELBERG · HEIDELBERGCoordinatorCity levelGermany

Links

Data: CORDIS, © European Union