Cholesterol-based lipophilic oligonucleotides incorporated into lipid membranes were Studied using solid-state NMR, differential scanning calorimetry, and fluorescence methods. Lipophilic oligonucleotides can be used to build nanotechnological structures oil membrane Surfaces, taking advantage of the specific Watson-Crick base pairing. We used a cholesteryl-TEG anchor first described by Pfeiffer and Hook (J. Am. Chem. Soc. 2004, 126, 10224-10225). The cholesterol-based anchor molecules were found to incorporate well into lipid membranes without disturbing the bilayer Structure and dynamics. In contrast to cholesterol, which is known to induce significant condensation of the membrane lipids, the cholesteryl-TEG anchor does not display this property. When the cholesteryl-TEG moiety was covalently bound to ail oligonucleotide, the resulting lipophilic DNA molecules inserted spontaneously into lipid membranes without altering their structure. The duplex formed by two complementary cholesteryl-TEG oligonucleotides had increased thermodynamic stability compared to the same oligonucleotides Without the anchor, both ill Solution and incorporated into lipid membranes. Since the cholesteryl-TEG anchor lacks the characteristic properties of cholesterol, oligonucleotides modified with this anchor are equally distributed between liquid-disordered and liquid-ordered domains in "raft" forming membranes. As ail example of ail application of these lipophilic oligonucleotides, cholesteryl-TEG-DNA was incorporated into Supported lipid bilayers formed oil polyelectrolyte-coated silica microparticles. The modified oligonucleotides were stably inserted into the lipid membrane and retained their recognition properties, therefore enabling further functionalization of the particles.