Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Jun 8;133(22):8392-5.
doi: 10.1021/ja2004736. Epub 2011 Apr 4.

Controlling and switching the morphology of micellar nanoparticles with enzymes

Ti-Hsuan Ku  1 , Miao-Ping Chien, Matthew P Thompson, Robert S Sinkovits, Norman H Olson, Timothy S Baker, Nathan C Gianneschi
Affiliations

Controlling and switching the morphology of micellar nanoparticles with enzymes

Ti-Hsuan Ku et al. J Am Chem Soc. .

Abstract

Micelles were prepared from polymer-peptide block copolymer amphiphiles containing substrates for protein kinase A, protein phosphatase-1, and matrix metalloproteinases 2 and 9. We examine reversible switching of the morphology of these micelles through a phosphorylation-dephosphorylation cycle and study peptide-sequence directed changes in morphology in response to proteolysis. Furthermore, the exceptional uniformity of these polymer-peptide particles makes them amenable to cryo-TEM reconstruction techniques lending insight into their internal structure.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Peptide-substrate polymeric amphiphiles assemble into spherical micelles. The peptide substrates within the micelle corona interact with enzymes to generate a variety of morphologies of polymeric amphiphile aggregates depending on the design of the peptide substrate and enzymes added.
Figure 2
Figure 2
TEM characterization of M1. (a) Micrograph of M1 sample, stained with 1% uranyl acetate. (b) Micrograph of unstained vitrified M1 sample. (c) Reconstructed radial density plot from cryo-TEM data (Supporting information, Figure 2S).
Figure 3
Figure 3
Response of M2 to sequential additions of PKA and PP1. (a) TEM and (b) SEM: M2 (20 μM with respect to polymer-peptide amphiphile) treated with PKA (2500 U) plus ATP (2 mM) and incubated at 30 °C for 24 hrs followed by dialysis. (c) TEM and (d) SEM: Phosphorylated particles subjected either to dialysis, or heat denaturation of PKA (20 min, 65 °C) prior to treatment with PP1 (2.5 U) for at 30 °C for 24 hrs. (e) DLS confirms increase and decrease of aggregate size in solution via phosphorylation and dephosphorylation respectively. (f) Phosphorylation and dephosphorylation were confirmed by radiolabelling the particles using [γ-32P] ATP. Heat denaturation and extended dialysis had no effect on M2 micelles alone. Note that no change is observed by DLS in the presence of ATP (2 mM) without addition of PKA.
Figure 4
Figure 4
Response of micelles M1 and M2 to treatment with MMPs. (a) TEM M1 + MMP-2. (b) SEM M1 + MMP-2. (c) TEM M2 + MMP-2. (d) SEM M2 + MMP-2. (e-f) DLS shown for particles indicating changes in particle size upon MMP treatment as indicated. Micelles at 20 μM (with respect to polymer-peptide amphiphile), were incubated with MMPs (100 μU) at 37 °C for 24 hrs (Tris-HCL, 50 mM, pH 7.4).
See this image and copyright information in PMC

References

    1. Torchilin VP. Coll Surf B. 1999;16:305–319.
    2. Shanmugananda Murthy K, Ma Q, Clark CG, Remsen EE, Wooley KL. Chem Commun. 2001:773–774.
    3. Hamley IW. Angew Chem, Int Ed. 2003;42:1692–1712. - PubMed
    4. Alarcon CdlH, Pennadam S, Alexander C. Chem Soc Rev. 2005;34:276–285. - PubMed
    5. Gothelf KV, LaBean TH. Org Biomol Chem. 2005;3:4023–4037. - PubMed
    6. Nayak S, Lyon LA. Angew Chem, Int Ed. 2005;44:7686–7708. - PubMed
    7. Petrak K. Drug Disc Today. 2005;10:1667–1673. - PubMed
    8. Vasir JK, Reddy MK, Labhasetwar VD. Curr Nanosci. 2005;1:47–64.
    9. Hawker CJ, Wooley KL. Science. 2005;309:1200–1205. - PubMed
    10. Mastrobattista E, van der Aa Marieke AEM, Hennink Wim E, Crommelin Daan JA. Nat Rev Drug Discov. 2006;5:115–121. - PubMed
    11. Na K, Sethuraman VT, Bae YH. Anti-Canc Agents Med Chem. 2006;6:525–535. - PubMed
    12. Alemdaroglu FE, Herrmann A. Org Biomol Chem. 2007;5:1311–1320. - PubMed
    13. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R. Nat Nanotechnol. 2007;2:751–760. - PubMed
    14. Smith D, Pentzer EB, Nguyen ST. Pol Rev. 2007;47:419–459.
    15. Ganta S, Devalapally H, Shahiwala A, Amiji M. J Cont Release. 2008;126:187–204. - PubMed
    16. Du J, O'Reilly RK. Soft Matter. 2009;5:3544–3561.
    17. Meng F, Zhong Z, Feijen J. Biomacromolecules. 2009;10:197–209. - PubMed
    1. Zhu L, Anslyn EV. Angew Chem, Int Ed. 2006;45:1190–1196. - PubMed
    2. Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Science. 1985;230:1350–1354. - PubMed
    3. Engvall E, Perlmann P. Immunochem. 1971;8:871–874. - PubMed
    1. Sawyers CL. Nature. 2008;452:548–552. - PubMed
    2. Vartak DG, Gemeinhart RA. J Drug Targ. 2007;15:1–20. - PMC - PubMed
    3. Raffetto JD, Khalil RA. Biochem Pharm. 2008;75:346–359. - PMC - PubMed
    4. Kessenbrock K, Plaks V, Werb Z. Cell. 2010;141:52–67. - PMC - PubMed
    5. Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S. Nature. 1980;284:67–68. - PubMed
    6. Davies B, Waxman J, Wasan H, Abel P, Williams G, Krausz T, Neal D, Thomas D, Hanby S, Balkwill F. Cancer Res. 1993;53:5365–5369. - PubMed
    7. MacDougall JR, Bani MR, Lin Y, Muschel RJ, Kerbel RS. Br J Cancer. 1999;80:504–512. - PMC - PubMed
    8. MacDougall JR, Bani MR, Lin Y, Rak J, Kerbel RS. Cancer Res. 1995;55:4174–4181. - PubMed
    9. Jinga DC, Blidaru A, Condrea I, Ardeleanu C, Dragomir C, Szegli G, Stefanescu M, Matache C. J Cell Mol Med. 2006;10:499–510. - PMC - PubMed
    10. Maatta M, Santala M, Soini Y, Turpeenniemi-Hujanen T, Talvensaari-Mattila A. Acta Obstet Gynecol Scand. 2010;89:380–384. - PubMed
    1. Israelachvilli JN, Mitchell DJ, Ninham BW. J Chem Soc, Faraday Trans 2. 1976;72:1525–1568.
    2. Tanford C. The Hydrophobic Effect: Formation of Micelles and Biological Membranes. Second. John Wiley & Sons, Inc; New York: 1980.
    3. Matsen MW, Bates FS. Macromolecules. 1996;29:7641–7644.
    4. Discher BM, Won YY, Ege DS, Lee JCM, Bates FS, Discher DE, Hammer DA. Science. 1999;284:1143–1146. - PubMed
    5. Nagarajan R. Langmuir. 2002;18:31–38.
    6. Jain S, Bates FS. Science. 2003;300:460–464. - PubMed
    7. Smart T, Lomas H, Massignani M, Flores-Merino MV, Perez LR, Battaglia G. Nano Today. 2008;3:38–46.
    1. Zhang L, Yu K, Eisenberg A. Science. 1996;272:1777–1779. - PubMed
    2. Bendejacq D, Ponsinet V, Joanicot M. Langmuir. 2005;21:1712–1718. - PubMed
    3. LaRue I, Adam M, Pitsikalis M, Hadjichristidis N, Rubinstein M, Sheiko SS. Macromolecules. 2006;39:309–314.
    4. Buetuen V, Liu S, Weaver JVM, Bories-Azeau X, Cai Y, Armes SP. React Funct Pol. 2006;66:157–165.
    5. Lee HI, Wu W, Oh JK, Mueller L, Sherwood G, Peteanu L, Kowalewski T, Matyjaszewski K. Angew Chem, Int Ed. 2007;46:2453–2457. - PubMed
    6. Ishihara Y, Bazzi HS, Toader V, Godin F, Sleiman HF. Chem Euro J. 2007;13:4560–4570. - PubMed
    7. Rijcken CJF, Soga O, Hennink WE, van Nostrum CF. J Cont Rel. 2007;120:131–148. - PubMed
    8. Nakayama M, Okano T. Macromolecules. 2008;41:504–507.
    9. Sundararaman A, Stephan T, Grubbs RB. J Am Chem Soc. 2008;130:12264–12265. - PubMed
    10. Klaikherd A, Nagamani C, Thayumanavan S. J Am Chem Soc. 2009;131:4830–4838. - PMC - PubMed
    11. Roy D, Cambre JN, Sumerlin BS. Chem Commun. 2009:2106–2108. - PubMed
    12. Wang YC, Tang LY, Li Y, Wang J. Biomacromolecules. 2009;10:66–73. - PubMed
    13. Moughton AO, O'Reilly RK. Chem Commun. 2010;46:1091–1093. - PubMed
    14. Agut W, Brulet A, Schatz C, Taton D, Lecommandoux S. Langmuir. 2010;26:10546–10554. - PubMed
    15. Chien MP, Rush AM, Thompson MP, Gianneschi NC. Angew Chem Int Ed. 2010;49:5076–5080. - PMC - PubMed

Publication types

MeSH terms