A DNA-based molecular probe for optically reporting cellular traction forces

Brandon L Blakely; Christoph E Dumelin; Britta Trappmann; Lynn M McGregor; Colin K Choi; Peter C Anthony; Van K Duesterberg; Brendon M Baker; Steven M Block; David R Liu; Christopher S Chen

doi:10.1038/nmeth.3145

A DNA-based molecular probe for optically reporting cellular traction forces

Nat Methods. 2014 Dec;11(12):1229-32. doi: 10.1038/nmeth.3145. Epub 2014 Oct 12.

Authors

Affiliations

¹ Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
² X-Chem, Inc., Waltham, Massachusetts, USA.
³ 1] Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA. [2] The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
⁴ 1] Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA. [2] Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts, USA.
⁵ Biophysics Program, Stanford University, Stanford, California, USA.
⁶ 1] Department of Biology, Stanford University, Stanford, California, USA. [2] Department of Applied Physics, Stanford University, Stanford, California, USA.
⁷ 1] Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA. [2] Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA. [3] The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.

Abstract

We developed molecular tension probes (TPs) that report traction forces of adherent cells with high spatial resolution, can in principle be linked to virtually any surface, and obviate monitoring deformations of elastic substrates. TPs consist of DNA hairpins conjugated to fluorophore-quencher pairs that unfold and fluoresce when subjected to specific forces. We applied TPs to reveal that cellular traction forces are heterogeneous within focal adhesions and localized at their distal edges.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Cell Adhesion / physiology*
Cells, Cultured
DNA Probes* / chemistry
Embryo, Mammalian / cytology
Embryo, Mammalian / metabolism
Fibroblasts / cytology
Fibroblasts / metabolism
Focal Adhesions / physiology*
Mechanotransduction, Cellular / physiology*
Mice
Microscopy, Fluorescence

Substances

DNA Probes

Abstract

Publication types

MeSH terms

Substances

Grants and funding