Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

New Design Paradigms: Tetraplex Building Blocks for Structural DNA Nanotechnology

For the most part DNA was considered Nature?s instruction manual to create and preserve life and hence the frequently employed description -- blueprint for life. However, DNA is now taking on a new aspect where it is finding use as a construction element for architecture on the nanoscale (1). This is aided by its predictable and specific recognition properties that give rise to a regular helical structure which behaves as a rigid rod on length scales upto ∼50 nm. Thus far, directed DNA assembly has relied on Watson-Crick base pairing, and this has been a powerful and preferred approach in structural DNA nanotechnology. I will discuss a paradigm shift in design and strategy that uses a four-stranded building block to create rigid scaffold and dynamic nanolevers. I describe how tetraplex building blocks give rise to organizations with far superior properties than their duplex DNA based counterparts and illustrates their hitherto untapped potential for structural DNA nanotechnology.

We have been interested in developing tetraplex building blocks for applications in structural DNA nanotechnology (2). I will describe a strategy to build rigid 1D scaffolds, called I-wires, using the i-tetraplex. The i-tetraplex consists of two parallel-stranded duplexes, each held together by C+H-C base pairs, intercalated in an anti-parallel orientation (3). High stability, attractive dimensions and structural uniformity make the I-wire a 1D scaffold that could overcome physical limitations associated with B-DNA. Furthermore, self assembly with this building block is amenable to control -- demonstrated by control over wire lengths using chemical ligation. This is aided by slow, templated structure growth that can be ?locked? at any time (4).

We have also used the i-tetraplex to construct a proton-sensitive DNA nanoelectro-mechanical system (NEMS). The NEMS senses a proton input, couples this to an i-tetraplex actuator and realizes nanomechanical motion. The estimated opening and closing forces are ∼ 9 pN, commensurate with cellular motor-proteins. We demonstrate the first intracellular application of DNA nanomotors by using the present NEMS to map spatiotemporal pH changes within cells (5).

References and Footnotes
  1. a) N. C. Seeman. Biochemistry 42, 7259-7269 (2003); b) S. Pitchiaya, Y. Krishnan. Chem. Soc. Rev. in press (2006).
  2. a) Y. Krishnan-Ghosh, E. Stephens, S. Balasubramanian. J. Am. Chem. Soc. 126, 5944-5945 (2004); b) Y. Krishnan-Ghosh, D. Liu, S. Balasubramanian. J. Am. Chem. Soc. 126, 11009-11016 (2004); c) Y. Krishnan-Ghosh, E. Stephens, S. Balasubramanian. Chem. Commun. 5278-5280 (2005); d) S. Modi, A. H. Wani, Y. Krishnan. Nucleic Acids Res. in press (2006). e) Chakraborty, S., Modi, S., Krishnan, Y. manuscript in preparation (2006).
  3. K. Gehring, J.-L. Leroy, M. GĂșeron. Nature 363, 561-564 (1993).
  4. Ghodke, H. B.; Vignesh, K.; Krishnan, R., Kumar, G. V. P.; Narayana, C.; Krishnan, Y. submitted (2006).
  5. Rangaraju, V., Krishnan, R., Krishnan, Y. manuscript in preparation (2006).

Harshad Ghodke
Ramya Krishnan
Vidhya Rangaraju
G. V. Pavan Kumar
Chandrabhas Narayana
Yamuna Krishnan*

National Centre for Biological Sciences
Bangalore 560 065, India