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Title: Switching of self-assembly in a peptide nanostructure with a specific enzyme

Abstract

Peptide self-assembly has been shown to be a useful tool for the preparation of bioactive nanostructures, and recent work has demonstrated their potential as therapies for regenerative medicine. In principle, one route to make these nanostructures more biomimetic would be to incorporate in their molecular design the capacity for biological sensing. We report here on the use of a reversible enzymatic trigger to control the assembly and disassembly of peptide amphiphile (PA) nanostructures. The PA used in these studies contained a consensus substrate sequence specific to protein kinase A (PKA), a biological enzyme important for intracellular signaling that has also been shown to be an extracellular cancer biomarker. Upon treatment with PKA, this PA molecule becomes phosphorylated causing the high aspect-ratio filamentous PA nanostructures to disassemble. Treatment with an enzyme to cleave the phosphate group results in reformation of the filamentous nanostructures. We also show that disassembly in the presence of PKA allows the enzyme-triggered release of an encapsulated cancer drug. In addition, these drug-loaded nanostructures were found to induce preferential cytotoxicity in a cancer cell line that is known to secrete high levels of PKA. This ability to control nanostructure through an enzymatic switch could allow for the preparationmore » of highly sophisticated and biomimetic materials that incorporate a biological sensing capability to enable therapeutic specificity.« less

Authors:
; ; ;  [1]
  1. NWU
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
UNIVERSITYNIH
OSTI Identifier:
1034184
Resource Type:
Journal Article
Journal Name:
Soft Matter
Additional Journal Information:
Journal Volume: 7; Journal Issue: (20) ; 2011
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; ASPECT RATIO; CAPACITY; DESIGN; ENZYMES; MEDICINE; NANOSTRUCTURES; NEOPLASMS; PEPTIDES; PHOSPHATES; PHOSPHOTRANSFERASES; PROTEINS; SPECIFICITY; SUBSTRATES

Citation Formats

Webber, Matthew J, Newcomb, Christina J, Bitton, Ronit, and Stupp, Samuel I. Switching of self-assembly in a peptide nanostructure with a specific enzyme. United States: N. p., 2012. Web. doi:10.1039/C1SM05610G.
Webber, Matthew J, Newcomb, Christina J, Bitton, Ronit, & Stupp, Samuel I. Switching of self-assembly in a peptide nanostructure with a specific enzyme. United States. https://doi.org/10.1039/C1SM05610G
Webber, Matthew J, Newcomb, Christina J, Bitton, Ronit, and Stupp, Samuel I. 2012. "Switching of self-assembly in a peptide nanostructure with a specific enzyme". United States. https://doi.org/10.1039/C1SM05610G.
@article{osti_1034184,
title = {Switching of self-assembly in a peptide nanostructure with a specific enzyme},
author = {Webber, Matthew J and Newcomb, Christina J and Bitton, Ronit and Stupp, Samuel I},
abstractNote = {Peptide self-assembly has been shown to be a useful tool for the preparation of bioactive nanostructures, and recent work has demonstrated their potential as therapies for regenerative medicine. In principle, one route to make these nanostructures more biomimetic would be to incorporate in their molecular design the capacity for biological sensing. We report here on the use of a reversible enzymatic trigger to control the assembly and disassembly of peptide amphiphile (PA) nanostructures. The PA used in these studies contained a consensus substrate sequence specific to protein kinase A (PKA), a biological enzyme important for intracellular signaling that has also been shown to be an extracellular cancer biomarker. Upon treatment with PKA, this PA molecule becomes phosphorylated causing the high aspect-ratio filamentous PA nanostructures to disassemble. Treatment with an enzyme to cleave the phosphate group results in reformation of the filamentous nanostructures. We also show that disassembly in the presence of PKA allows the enzyme-triggered release of an encapsulated cancer drug. In addition, these drug-loaded nanostructures were found to induce preferential cytotoxicity in a cancer cell line that is known to secrete high levels of PKA. This ability to control nanostructure through an enzymatic switch could allow for the preparation of highly sophisticated and biomimetic materials that incorporate a biological sensing capability to enable therapeutic specificity.},
doi = {10.1039/C1SM05610G},
url = {https://www.osti.gov/biblio/1034184}, journal = {Soft Matter},
number = (20) ; 2011,
volume = 7,
place = {United States},
year = {Wed Mar 14 00:00:00 EDT 2012},
month = {Wed Mar 14 00:00:00 EDT 2012}
}