K Towles, JF Beausang, PC Nelson, et al.
Cells need to turn genes on and off, e.g. in response to external conditions. Gene regulation in bacteria can involve the formation of loops in DNA, by the binding of regulatory proteins, for example lac repressor (green complex left). Understanding this mechanism is important if we wish to “program” bacteria to perform useful tasks, disrupt pathogenic bacteira, and so on.
But it’s hard to study the operation of these nanoscale control devices in vivo! Tethered particle motion reconstitutes the desired behavior in solution, then infers the behavior of the invisible DNA from that of an attached bead (yellow right).
The molecular “leash” releases when the loop breaks down, allowing greater bead motion, then tightens as the loop re-forms. We can find the thermodynamics and even kinetics of DNA looping in this way, and see how they depend on tether length, presence of drugs, etc.