Molecular Bioengineering – Developing Molecular Tension Sensors


Knowing the force response characteristics of the tension sensor module (TSM) is key to a conclusive molecular force measurement. Therefore, we have carefully calibrated our FRET modules (including donor and acceptor fluorophore) by single-molecule force spectroscopy to determine critical molecular properties including folding/unfolding transition pathways, reversibility, and force sensitivity. These experiments demonstrated that our TSMs respond very quickly (in the millisecond to sub-millisecond timescale) to applied mechanical loads, and they quickly refold once forces are reduced. Importantly, the folding/unfolding transitions are hysteresis free, allowing unambiguous FRET–force measurements. At this point, four calibrated biosensors are available that respond to distinct force ranges; please click for detailed information: F40, FL, HP35 and HP35st. This molecular toolbox allows the evaluation of physiologically relevant forces that act across individual molecules in living cells.

© Uni MS - Prof. Dr. C. Grashoff


Selected publications:

Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA. Nature. 2010 Jul 8; 466:263-266. >>

Austen K, Ringer P, Mehlich A, Chrostek-Grashoff A, Kluger C, Klingner C, Sabass B, Zent R, Rief M, Grashoff C. Nat Cell Biol. 2015 Dec; 17(12):1597-1606. [Epub 2015 Nov 2] >>

Freikamp A, Cost AL, Grashoff C. Trends Cell Biol. 2016 Nov; 26(11):838-847. [Epub 2016 Aug 17] >>

Ringer P, Weißl A, Cost AL, Freikamp A, Sabass B, Mehlich A, Tramier M, Rief M, Grashoff C. Nature Methods 2017 Nov; 14(11):1090-1096. [Epub 2017 Sep 18] >>