pH as a Trigger of Peptide β-Sheet Self-Assembly and Reversible Switching between Nematic and Isotropic Phases

• Published in: Journal of the American Chemical Society Vol. 125; no. 32; pp. 9619 - 9628
• Main Authors: Aggeli, Amalia, Bell, Mark, Carrick, Lisa M, Fishwick, Colin W. G, Harding, Richard, Mawer, Peter J, Radford, Sheena E, Strong, Andrew E, Boden, Neville
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 13.08.2003; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Condensed matter: structure, mechanical and thermal properties; Equations of state, phase equilibria, and phase transitions; Exact sciences and technology; Gels - chemistry; Glutamine - chemistry; Hydrogen-Ion Concentration; Oligopeptides - chemistry; Physical Sciences; Physics; Protein Structure, Secondary; Science & Technology; Specific phase transitions; Static Electricity; Thermodynamics; Transitions in liquid crystals; HYDROGELS; ALPHA-HELIX; FIBRILS; GELS; SPECTROSCOPY; STRUCTURAL BASIS; STABILITY; PROTEINS; TITRATION; AGGREGATION; Infrared spectroscopy; Shear viscosity; Molecular orientation; Phase transformations; Isotropic structure; Experimental study; N terminal peptide; NMR spectroscopy; Acid base titration; Nematic crystals; Organic compounds; Rheological properties
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja021047i

The hierarchical self-assembly of rationally designed synthetic peptides into β-sheet tapes, ribbons, fibrils, and fibers opens up potentially useful routes to soft−solidlike materials such as hydrogels, organogels, or liquid crystals. Here, it is shown how incorporation of Glu (−CH2CH2COOH) or Orn (−CH2CH2CH2NH2) into the primary structure of an 11 amino acid peptide enables self-assembly to be rapidly (seconds) and reversibly controlled by simply changing pH. Solutions of monomeric peptide, typically at concentrations in excess of 0.003 v/v, can be switched within seconds to, for example, nematic gel states comprised of interconnected orientationally ordered arrays of fibrils or vice versa. This is to be compared with the lyophilized peptide dissolution route to nematic fluids and gels which is impracticably long, taking many hours or even days. An important design principle, that stabilization of fibrillar dispersions requires of the order of one unit of net positive or negative charge per peptide molecule, is first demonstrated and then used to design an 11 amino acid peptide P11-3 (CH3CO-Gln-Gln-Arg-Phe-Gln-Trp-Gln-Phe-Gln-Gln-Gln-NH2) whose self-assembly behavior is independent of pH (1 < pH < 10). pH control is then incorporated by appropriately positioning Glu or Orn side chains so that the peptide−peptide free energy of interaction in the tapelike substructure is strongly influenced by direct electrostatic forces between γ-COO- in Glu- or δ-NH3 + in Orn+, respectively. This design principle is illustrated by the behavior of two peptides:  P11-4 (CH3CO-Gln-Gln-Arg-Phe-Glu-Trp-Glu-Phe-Glu-Gln-Gln-NH2) which can be switched from its nematic to its isotropic fluid state by increasing pH and P11-5 (CH3CO-Gln-Gln-Orn-Phe-Orn-Trp-Orn-Phe-Gln-Gln-Gln-NH2) designed to exhibit the converse behavior. Acid−base titrations of fibrillar dispersions reveal deprotonation of the γ-COOH of Glu or of the δ-NH3 + of Orn+ occurs over wide bands of up to 5 pH units, a feature of polyelectrolytes. The values of the energy parameters controlling self-assembly can therefore be smoothly and continuously varied by changing pH. This enables isotropic fluid-to-nematic transitions to be triggered by relatively small additions of acid or base, typically 1 part in 103 by volume of 1 M HCl or NaOH.