the complex disintegrates. The increase of the ionic strength results in a reduction of the electrostatic repulsion shifting the equilibrium towards re-association of the tetramer. We have shown that, in contrast to short G-qaudruplexes reported earlier (4,13), long mono- molecular G-quadruplexes can be formed in the absence of K+ and Na+ cations (18). This is true also for the long tetra-molecular G4 structures reported here. The struc- tures made in the absence of these ‘stabilizing’ ions, but in the presence of nonstabilizing Li+ are stable and do not undergo any observable change in aqueous solution for weeks. Addition of the ions to the molecules alters the CD spectrum of the DNA (Figure 8). The eﬀect of K+ and Na+ on the CD properties of G4-DNA reﬂects changes in the ﬁne structure of the molecules induced, by the cations. The molecular morphology and the CD spectrum of tetra-molecular G-quadruplexes measured here are diﬀer- ent from those reported earlier for mono-molecular G4-wires (18). The height of the former structures is nota- bly larger than that of mono-molecular G-quadruplexes (insets of Figure 6A and B). The CD spectra of both types of molecules are also very diﬀerent (Figure 8). These results are consistent with the diﬀerent pro- perties of short mono- and tetra-molecular telomeric G-quadruplexes reported in the literature (13,14). A con- clusive explanation of the greater height of tetra-molecular G-quadruplexes compared to mono-molecular ones can only be given by X-ray or NMR data, which are not avail- able for these molecules due to their complexity and only recent availability. It may originate from a stronger struc- tural stability when all the four strands run in 30–50 direc- tion rather than when every two strands run in opposite directions. Another possible explanation is that a frag- ment in the tetra-molecular structure located close to the site of avidin attachment is encapsulating the protein. This greater height indicates a higher resistance of the tetra- molecular structures to deformations caused by an inter- action of the molecules with the mica surface and with the AFM cantilever than that of the mono-molecular G4-DNA. We have shown by EFM, (Figure 9) that tetra-molecular G-quadruplexes are characterized by a clear polarizability which is indicative of possible electrical conductivity. The high resistance of the tetra-molecular G-quadruplexes to mechanical deformations together with their electrical polarizability makes these structures very promising for nanoelectronic applications. ACKNOWLEDGEMENTS This work was supported by the EC through contracts IST-2001-38951 (‘DNA-Based Nanowires’) and FP6- 029192 (‘DNA-Based Nanodevices’). 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