Seminars Archive

Transducing biomolecular interactions into nanomechanics

Abstract
Microcantilevers (MCs) are versatile micro-electro-mechanical systems (MEMS). In the last few years they have been implemented for nanomechanical transduction of biochemical interactions [1], allowing for sensitive, label-free, direct, real-time and multiplexed detection of biomolecules as well as for investigations of biomolecule fundamental properties [2]. MCs are typically 0.2-3 micron thick, 20-100 micron wide and 100-800 micron long, and are connected to one end to an appropriate support, resembling a diving board. In biosensing, MCs are functionalized with a probe (receptor) that can selectively bind the target species (ligands). Specific adsorption of the targets induces a nanomechanical response of the MC, that provides the transduction/sensing mechanism. The read-out of the response is commonly achieved by an optical lever or a piezoresistive film integrated with the MC. On the base of the MC functionalization geometry and actuation mode, the nanomechanical response can be (i) bending of the MC induced by the surface stress that originates from binding of the targets with the probes immobilized onto one face of the MC (static mode); (ii) changes in the eigenfrequencies of the MC upon target mass load (dynamic mode) [2]. Remarkably, the first response/transduction mode is energy-based, viz. it is directly related to the free energy involved in target-probe binding [3]. MCs may reach absolute sensitivities down to attograms, that are comparable with those of more mature biosensors, such as Surface Plasmon Resonance (SPR) spectroscopy and acoustic sensors, including Quartz Crystal Microbalances (QCM). Furthermore, MCs can play a key role in critical molecular recognition experiments and other fundamental biophysicochemical investigations. For example, thanks to direct mechanical transduction of the free energy involved in the binding reactions, they constitute a promising alternative for detection of low molecular weight (LMW) species [4] and allow for investigation of protein conformational changes [5] or cooperative work of molecular motors [6]. After introducing the physicochemical basics and the key applications of MC molecular recognition, the seminar will cover our recent results on the subject, including theoretical insights [3], novel functionalization routes [7,8] and preliminary results on drug screening. [1] J. Fritz et al. Science 288 (2000) 316. [2] P.S. Waggoner et al. Lab Chip 7 (2007) 1238. [3] P. Bergese et al. J. Coll. Int. Sci. 316 (2007) 1017. [4] P. Bergese et al. Curr. Med. Chem. 15 (2008) 1706. [5]T. Braun et al. Biophys. J. 90 (2006) 2970. [6] W. Shu et al. J. Am. Chem. Soc. 127 (2005) 17054. [7] P. Bergese et al. Appl. Surf. Sci. 253 (2007) 4226. [8] G. Oliviero et al. Anal. Chim. Acta 630 (2008) 161.