Community Research and Development Information Service - CORDIS

  • European Commission
  • CORDIS
  • Projects and Results
  • Final Report Summary - TIPS4CELLS (Scanning probe microscopy techniques for real-time, high-resolution imaging and molecular recognition in functional and structural genomics)
FP6

TIPS4CELLS Report Summary

Project ID: 512101
Funded under: FP6-LIFESCIHEALTH
Country: Netherlands

Final Report Summary - TIPS4CELLS (Scanning probe microscopy techniques for real-time, high-resolution imaging and molecular recognition in functional and structural genomics)

The ultimate aim of the TIPS4CELLS project was to develop new imaging tools, based on Atomic force microscopy (AFM), which would enable the study of multi-protein complexes in their native environment at unprecedented sensitivity and resolution. Unfortunately, AFM cannot image all samples at atomic resolution. Due to the fact that biological structures are soft, the tip-sample interaction tends to distort or destroy the object of interest. In this project techniques were developed that overcome these problems and allow imaging at a higher resolution. Specifically, the research focused on further developing Scanning probe microscopy (SPM) because of its high-lateral resolution and sensitive force detection capability. Furthermore, new technologies, such as faster Scanning force microscopy (SFM) at lower forces improved tip chemistry and integration of optical imaging techniques would be used to analyse ligand-receptor interactions in the plasma membrane and in downstream signalling events in living cells, and also to study the structure, transport and dynamics of Nuclear pore complexes (NPC) in functional nuclei.

Various technical improvements necessary were implemented and tested. Some of them such as the improved linker chemistries and the integration of fluorescence microscopy were applied to the study of living cells while others such as the high speed imaging and carbon nanotube tips were applied to the study of NPC, yielding exciting scientific results. By operating High-speed AFM (HS AFM) in air, speeds of 1 300 frames / second were achieved compared with conventional AFM at around 2 minutes / frame. The HS AFM maximum line rate to date was 200 000 lines / second. The project aimed to provide a better understanding of the mechanism involved in this high-speed imaging that prevents catastrophic damage to the specimen. Tribological data pointed to a super lubrication effect in which the tip was lifted off the surface by the hydrostatic pressure generated by moving through a viscous fluid (water). It was found that adverse hydrodynamic effects associated with the cantilever moving at high speeds totally immersed in water prevented the routine use of HS AFM in liquids. However, a better understanding of the frequency and speed dependence of these effects allowed routinely imaging most samples in aqueous environments. Even large and complex biological structures such as cells and chromosomes could be imaged in liquid at video frames rates.

Related information

Contact

Tjerk Hendrik OOSTERKAMP, (Group Leader)
Tel.: +31-715-275-424
Fax: +31-715-275-404
E-mail
Follow us on: RSS Facebook Twitter YouTube Managed by the EU Publications Office Top