Exploring locked nucleic acids as a bio-inspired materials assembly and disassembly tool

Abstract

Oligonucleotides hold great promise as a recognition-based biomaterials assembly and disassembly tool. Chemically modified oligonucleotides such as locked nucleic acids (LNA) provide the added advantage of nuclease resistance. In the current study, we focus on programming the assembly and disassembly of LNA-linked colloidal particles as a function of sequence composition. We find that incorporation of LNA residues (∼30%) into either one or both primary hybridization partner strands results in a higher duplex density than for isosequential DNA strands. Mismatched primary hybridization partners with sequence length of 11–15 bases have similar initial primary duplex densities. The displacement of mismatched strands by 15 base-long, perfectly matched competitive target strands, however, does depend on the base length of the original mismatched partner strand. Confocal microscopy confirms that substantial colloidal assembly occurs for both perfectly matched and mismatched LNA sequences that are 9 bases in length. Extensive disassembly for the mismatched case is then triggered through the introduction of 15 base-long competitive target strands. Our work demonstrates that LNA can be used to programmatically assemble and disassemble colloidal particles.