Regulation of Gene-Expression by Mechanical Force, RNA structure, Optical Tweezers

Biological Physics and Biology One Molecule at a Time

Optical tweezers are ideally suited for probing the effects of force upon biological processes. I have previously pioneered the so-called optical force clamp, a feedback-controlled optical tweezers that maintains a constant force upon a single moving motor protein (Visscher et al., Nature 400, 184-189). While at the University of Arizona research has focused on the role of mechanical force in the regulation of gene-expression. We not only investigate how tension in DNA controls initiation of transcription by T7 RNA polymerases, but also how it affects the translocation of ribosomes along mRNA, and how force unfolds downstream mRNA structures known to cause translational recoding (-1 frameshifting).

For example the unfolding of the HIV-1 RNA hairpin that triggers -1 frameshifting can be observed at a force of ~15 pN by stretching it using optical tweezers (See figure on the right.)