ABSTRACT
A mechanistic understanding of fundamental cancer processes requires a detailed knowledge not only of the underlying biochemistry but also of the accompanying structural changes in the biopolymers involved and of the interplay between “chemical” and “mechanical” changes. Some cancer-relevant molecular processes, for instance, in cell signaling, gain complexity from the fact that multiple components interact with each other in a time-dependent fashion.1 The investigation of these intrinsically dynamic processes is difcult since it requires the ability to detect and quantify distance and position changes on nanometer length scales in real time. Ideally, these measurements are performed with single molecule sensitivity to bypass the need for ensemble synchronization and to access short-lived intermediates.2,3 Since the wave nature of light limits the resolution of conventional light microscopy to approximately 400 nm in the visible, the investigation of nanometer distance changes in individual biopolymers in real time using an optical microscope requires special techniques, such as •uorescence resonance energy transfer (FRET),4,5 two color colocalization,6-8 or nanometal surface energy transfer9 between noble metal nanoparticles
12.1 Introduction .................................................................................................................................. 209 12.2 Materials .......................................................................................................................................211 12.3 Methods .........................................................................................................................................212
