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

Matthew J. Webber, Christina J. Newcomb, Ronit Bitton, Samuel I Stupp

Research output: Contribution to journalArticle

93 Citations (Scopus)

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 preparation of highly sophisticated and biomimetic materials that incorporate a biological sensing capability to enable therapeutic specificity.

Original languageEnglish
Pages (from-to)9665-9672
Number of pages8
JournalSoft Matter
Volume7
Issue number20
DOIs
Publication statusPublished - Oct 21 2011

Fingerprint

Self assembly
peptides
self assembly
enzymes
Nanostructures
Amphiphiles
Peptides
Cyclic AMP-Dependent Protein Kinases
proteins
Enzymes
cancer
biomimetics
drugs
preparation
biomarkers
Biomimetic materials
activity (biology)
high aspect ratio
medicine
cultured cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Condensed Matter Physics

Cite this

Switching of self-assembly in a peptide nanostructure with a specific enzyme. / Webber, Matthew J.; Newcomb, Christina J.; Bitton, Ronit; Stupp, Samuel I.

In: Soft Matter, Vol. 7, No. 20, 21.10.2011, p. 9665-9672.

Research output: Contribution to journalArticle

Webber, Matthew J. ; Newcomb, Christina J. ; Bitton, Ronit ; Stupp, Samuel I. / Switching of self-assembly in a peptide nanostructure with a specific enzyme. In: Soft Matter. 2011 ; Vol. 7, No. 20. pp. 9665-9672.
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