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Search processes on small scales: What we can learn about cellular processes from single molecule experiments

Prof. Ralf Metzler,
TU Munich

Facilitated diffusion of regulatory proteins for a specific binding site
on a DNA molecule consisting of megabases of base-pairs combines 3D volume
diffusion with 1D motion along the DNA. The latter is mediated by so-called
non-specific binding, a finite binding affinity to DNA also at segments,
that are not the specific binding site. The combination of these two
mechanisms significantly speeds up the search. In addition, intersegmental
transfers that occur at contact points of chemically remote segments of the
DNA due to looping gives rise to Levy flights along the DNA that further
optimise the search.
While this model holds for diluted in vitro solutions, in the
cell molecular crowding occurs, leading to the subdiffusion of larger
molecules. Consequences of this effect to the search process will be
discussed, in particular, due to the resulting weak ergodicity breaking.

Information about these search models may be obtained from single molecule
experiments. Results from optical tweezers and AFM studies related to
gene regulation will be discussed.