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Author Notes:

To whom correspondence should be addressed. E-mail: thomas.barker@bme.gatech.edu

Author contributions: L.C., H.B., and T.H.B. designed research;

L.C., M.K.Z., V.F.F., and P.S. performed research;

L.C., V.F.F., H.B., and T.H.B. analyzed data;

and L.C., H.B., and T.H.B. wrote the paper.

We thank Drs. Treniece Terry and Michael Smith for enlightening discussions and helpful suggestions.

The authors declare no conflict of interest.

Subjects:

Research Funding:

This work was supported by National Institutes of Health (NIH) T32-GM008433 and NIH T32-EB006343 training grants to L.C., an Armstrong Fund for Science award to H.B., and a Georgia Tech Integrative BioSystems Institute seed grant to T.H.B.

Keywords:

  • Amino Acid Sequence
  • Animals
  • Bacteriophages
  • Cells, Cultured
  • Cellular Microenvironment
  • Extracellular Matrix
  • Fibroblasts
  • Fibronectins
  • Integrins
  • Lung
  • Mechanotransduction, Cellular
  • Mice
  • Microscopy, Confocal
  • Models, Molecular
  • Molecular Probes
  • Peptide Library
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Unfolding

Phage-based molecular probes that discriminate force-induced structural states of fibronectin in vivo

Tools:

Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 109, Number 19

Publisher:

, Pages 7251-7256

Type of Work:

Article | Final Publisher PDF

Abstract:

Applied forces and the biophysical nature of the cellular microenvironment play a central role in determining cellular behavior. Specifically, forces due to cell contraction are transmitted into structural ECM proteins and these forces are presumed to activate integrin "switches." The mechanism of such switches is thought to be the partial unfolding of integrin-binding domains within fibronectin (Fn). However, integrin switches remain largely hypothetical due to a dearth of evidence for their existence, and relevance, in vivo. By using phage display in combination with the controlled deposition and extension of Fn fibers, we report the discovery of peptidebased molecular probes capable of selectively discriminating Fn fibers under different strain states. Importantly, we show that the probes are functional in both in vitro and ex vivo tissue contexts. The development of such tools represents a critical step in establishing the relevance of theoretical mechanotransduction events within the cellular microenvironment.

Copyright information:

© Cao et al.

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