Single-molecule optical microscopy provides average-free, dynamical and structural information about condensed matter at molecular scales. Single fluorescent molecules can now be located and tracked with a spatial resolution as high as a few tens of nanometers, even at depths as large as several microns. These capabilities are ideal to link the macroscopic physical properties of soft condensed matter with the structure, organization and dynamics of the constituent molecules. Perhaps the most surprising conclusion drawn from single-molecule observations is the unsuspected heterogeneity of molecular assemblies, both in time and space, which had remained largely hidden in conventional ensemble experiments. The structural glass transition is said to be one of the hardest open problems in condensed matter science. Although most agree on the crucial part played by heterogeneity in this process, the guesses vary wildly as to the scale and relaxation times of the inhomogeneities. Our recent discovery of glassy rheology in supercooled glass formers, following earlier observations of heterogeneity, has been received with much interest in the complex liquids community. I am convinced that single-molecule studies have the potential to radically change our view of supercooled liquids and glasses. In a broader sense, molecular insight from chemical physics complements the general ideas developed by statistical physicists. I believe it is the missing link toward a molecular control of the physical properties of soft materials. I propose to perform a broad range of novel single-molecule experiments using a micro-rheological cell to apply mechanical stress, strains and/or temperature jumps. In particular, we will perform mechanical studies of solid-solid friction, and temperature-jump studies of single proteins and single protein complexes.
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