In order to design soft coatings, surface tethering of vesicular structures self-assembled from oligonucleotide-polymer hybrids is achieved through hybridization. Watson-Crick base-pairing occurs between the nucleotide sequences involved in the self-assembly and their surface-tethered complementary sequences. Combining the quartz crystal microbalance and in situ observations using confocal laser scanning microscopy, it is evidenced that the vesicles retain their morphology even under flow stress. Surprisingly, these soft surfaces prevent bacterial colonization.