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Abstract Supramolecular self‐assembly in biological systems holds promise to convert and amplify disease‐specific signals to physical or mechanical signals that can direct cell fate. However, it remains challenging to design physiologically stable self‐assembling systems that demonstrate tunable and predictable behavior. Here, the use of zwitterionic tetrapeptide modalities to direct nanoparticle assembly under physiological conditions is reported. The self‐assembly of gold nanoparticles can be activated by enzymatic unveiling of surface‐bound zwitterionic tetrapeptides through matrix metalloprotease‐9 (MMP‐9), which is overexpressed by cancer cells. This robust nanoparticle assembly is achieved by multivalent, self‐complementary interactions of the zwitterionic tetrapeptides. In cancer cells that overexpress MMP‐9, the nanoparticle assembly process occurs near the cell membrane and causes size‐induced selection of cellular uptake mechanism, resulting in diminished cell growth. The enzyme responsiveness, and therefore, indirectly, the uptake route of the system can be programmed by customizing the peptide sequence: a simple inversion of the two amino acids at the cleavage site completely inactivates the enzyme responsiveness, self‐assembly, and consequently changes the endocytic pathway. This robust self‐complementary, zwitterionic peptide design demonstrates the use of enzyme‐activated electrostatic side‐chain patterns as powerful and customizable peptide modalities to program nanoparticle self‐assembly and alter cellular response in biological context.
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Phosphobisaromatic motifs enable rapid enzymatic self-assembly and hydrogelation of short peptides
Enzyme-instructed self-assembly (EISA) and hydrogelation is a versatile approach for generating soft materials. Most of the substrates for alkaline phosphatase catalysed EISA utilize phosphotyrosine ( p Tyr) as the enzymatic trigger for EISA and hydrogelation. Here we show the first example of phosphonaphthyl ( p NP) and phosphobiphenyl ( p BP) motifs acting as faster enzymatic triggers than phosphotyrosine for EISA and hydrogelation. This work illustrates novel enzyme triggers for rapid enzymatic self-assembly and hydrogelation.
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- Award ID(s):
- 1827820
- PAR ID:
- 10330944
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 17
- Issue:
- 38
- ISSN:
- 1744-683X
- Page Range / eLocation ID:
- 8590 to 8594
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d1sm01221e
