The goal is to develop a nanofluidic platform for single molecule biophysics studies of DNA/protein complexes and amyloid fibrils under strong confinement. In nanofluidics biomacromolecules are generally visualized using fluorescence microscopy but we suggest that nanoplasmonics might be a suitable complement for totally label-free detection. Shifts in the dark-field extinction spectrum of a metal nanoparticle placed in close proximity to a nanochannel when a biomacromolecule passes can be used for studies with high spatial and temporal resolution. While the nanofluidic platform is useful for studies of a variety of DNA/protein interactions, an initial focus is how proteins involved in recombination affect physical properties of DNA. RecA-DNA filaments have a persistence length that is more than 10 times longer than for pure DNA, and are anticipated to show vastly different polymer physics in nanochannels compared to DNA. Moreover, we will study how amyloid fibrils, the pathological hallmark of several diseases including Alzheimer´s disease, behave under strong confinement. We will vary properties such as the nature of the native protein they are formed from and the surrounding environment. In particular, the effect of confinement on formation of the prefibrillar structures that are believed to be the most toxic species in protein misfolding diseases will be studied in detail.
Professor at Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry
Funding Chalmers participation during 2012–2015