ARC Nanoforce

Extreme miniaturization is made necessary by the steadily increasing requirements of information technologies and smart sensors, which are expected not only to detect and quantify the presence of a substance but also to handle in situ, in a simple way, the information obtained [1-5]. The implementation of physical systems able to handle the information at the nanometric and molecular scales calls for a strong basic effort aiming at a better understanding of the forces governing at those scales the interactions between the constitutive subunits and between the latter and the substrate.

The main goal of this multidisciplinary ARC proposal is to contribute to the characterization, the control and the use of these interactions for the implementation of smart sensors and molecular logic machines, and for the patterning of surfaces. Molecular recognition is one of the cornerstones of these devices. The model systems that we propose to investigate will extensively use the molecular recognition and self-assembling properties of biological systems, in particular of nucleic bases. We will focus on hybrid complexes where DNA or RNA oligomers are anchored on gold clusters, nanoparticles, and surfaces. Gold is a standard support for devices in many technological and diagnostic applications. The interactions between DNA or RNA and gold are among the most interesting ones for the implementation of smart sensors because they are tuned by the molecular recognition processes that either govern the pairing of nucleic bases (Watson-Crick bonds) or are responsible for the emergence of more complex structures like guanine quadruplexes (Hoogsteen bonds). These structures are of central importance because they might play an essential role in the regulation of many biological processes. The same interactions can be used for encoding patterns on surfaces and for logic operation implementations.

We intend to characterize in detail the interactions between gold and molecular model systems starting from the simplest ones – the nucleic bases – and moving progressively to more complex oligonucleotides of increasing size (a few bases up to about ten bases). The influence of the gold morphology (flat or rough surfaces, nanoparticles, clusters of various sizes) and of its charge state will be investigated. In addition, we will explore how the interactions between gold and the bases, oligonucleotides, and Watson-Crick base pairs, can be tuned by the presence of inorganic cations, intercalators, or ligands in the minor or major groove. Another effect that we plan to study is the role of base methylation in the recognition process between complementary strands.

Complementary investigation techniques and methods will be used:

·    Characterization of the interactions between the isolated subunits in the gas phase and of the same systems anchored on a surface by mass spectrometry,

·    Theoretical modelling of the properties of these systems at the molecular level,

·    Evaluation of the interaction forces in the systems anchored on a surface at the molecular level by single molecule force spectroscopy via techniques derived from atomic force microscopy (AFM).

Once the systems have been carefully characterized, the tuning and control of interactions between gold and oligonucleotides and between complementary strands will be used to demonstrate the feasibility of encoding patterns on surfaces and of implementing smart sensors and logic operations through the manipulation of bond patterns, transport and targeted delivery of individual objects (such as oligonucleotide-decorated gold nanoparticles) using an AFM tip and playing with the object/substrate and object/AFM tip interaction forces.