title: Mechanism of the pH-Controlled Self-Assembly of Nanofibers from Peptide Amphiphiles.
abstract: Stimuli-responsive, self-assembling nanomaterials hold a great promise to revolutionize medicine and technology. However, current discovery is slow and often serendipitous. Here we report a multiscale modeling study to elucidate the pH-controlled self-assembly of nanofibers from the peptide amphiphiles, palmitoyl-I-A3E4-NH2. The coarse-grained simulations revealed the formation of random-coil based spherical micelles at strong electrostatic repulsion. However, at weak or no electrostatic repulsion, the micelles merge into a nanofiber driven by the β-sheet formation between the peptide segments. The all-atom constant pH molecular dynamics revealed a cooperative transition between random coil and β-sheet in the pH range 6-7, matching the CD data. Interestingly, although the bulk pKais more than one unit below the transition pH, consistent with the titration data, the highest pKa's coincide with the transition pH, suggesting that the latter may be tuned by modulating the pKa's of a few solvent-buried Glu side chains. Together, these data offer, to our best knowledge, the first multiresolution and quantitative view of the pH-dependent self-assembly of nanofibers. The novel protocols and insights gained are expected to advance the computer-aided design and discovery of pH-responsive nanomaterials.
authors.affiliation: The Institute of Genetics and Molecular and Cellular Biology , 67404 Illkirch Cedex, France.
authors.forename: Yoann
authors.initials: Y
authors.lastname: Cote
authors.affiliation: Department of Chemical Engineering and Materials Science, The Henry Samueli School of Engineering, University of California , Irvine, California 92697, United States.
authors.forename: Iris W
authors.initials: IW
authors.lastname: Fu
authors.affiliation: Department of Chemistry, Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Dobson
authors.affiliation: Department of Chemistry, Ohio State University , Columbus, Ohio 43210, United States.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Goldberger
authors.affiliation: Department of Chemical Engineering and Materials Science, The Henry Samueli School of Engineering, University of California , Irvine, California 92697, United States.
authors.forename: Hung D
authors.initials: HD
authors.lastname: Nguyen
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland , Baltimore, Maryland 21201, United States.
authors.forename: Jana K
authors.initials: JK
authors.lastname: Shen
references.citation: Angew Chem Int Ed Engl. 2011 Jul 4;50(28):6292-5
references.pmid: 21626619
references.citation: J Chem Phys. 2012 Nov 14;137(18):184105
references.pmid: 23163362
references.citation: Adv Healthc Mater. 2013 Oct;2(10):1388-400
references.pmid: 23554376
references.citation: Nature. 1993 Mar 18;362(6417):267-70
references.pmid: 8459852
references.citation: Nat Mater. 2013 Nov;12(11):991-1003
references.pmid: 24150417
references.citation: J Am Chem Soc. 2003 Aug 13;125(32):9619-28
references.pmid: 12904028
references.citation: J Chem Theory Comput. 2012 Sep 11;8(9):3257-3273
references.pmid: 23341755
references.citation: Protein Sci. 2004 Nov;13(11):2909-24
references.pmid: 15498937
references.citation: Proteins. 2004 Sep 1;56(4):738-52
references.pmid: 15281127
references.citation: J Phys Chem B. 2008 Feb 28;112(8):2326-34
references.pmid: 18251531
references.citation: Protein Sci. 1992 Feb;1(2):227-35
references.pmid: 1304905
references.citation: Bioinformatics. 2013 Apr 1;29(7):845-54
references.pmid: 23407358
references.citation: Biomaterials. 2008 Dec;29(34):4501-9
references.pmid: 18774605
references.citation: Proteins. 2001 Aug 15;44(3):344-60
references.pmid: 11455608
references.citation: Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697
references.pmid: 9895674
references.citation: Biopolymers. 2010;94(1):1-18
references.pmid: 20091874
references.citation: J Chem Theory Comput. 2011 Aug 9;7(8):2617-29
references.pmid: 26606635
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 16;101(46):16180-5
references.pmid: 15534217
references.citation: Proteins. 1994 Mar;18(3):267-80
references.pmid: 8202468
references.citation: J Comput Chem. 2009 Jul 30;30(10):1545-614
references.pmid: 19444816
references.citation: Langmuir. 2013 Dec 3;29(48):14823-30
references.pmid: 24215478
references.citation: Nano Lett. 2012 Sep 12;12(9):4907-13
references.pmid: 22924639
references.citation: Science. 2001 Nov 23;294(5547):1684-8
references.pmid: 11721046
references.citation: Biopolymers. 1983 Dec;22(12):2577-637
references.pmid: 6667333
references.citation: Proteins. 1995 Dec;23(4):566-79
references.pmid: 8749853
references.citation: J Am Chem Soc. 2012 Feb 29;134(8):3647-50
references.pmid: 22309293
references.citation: Biophys J. 2005 Jul;89(1):141-57
references.pmid: 15863480
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5133-8
references.pmid: 11929981
references.citation: J Am Chem Soc. 2011 Mar 16;133(10):3677-83
references.pmid: 21341770