Pushing and Pulling: A Dual pH Trigger Controlled by Varying the Alkyl Tail Length in Heme Coordinating Peptide Amphiphiles

Abstract

Some organisms in nature that undergo anaerobic respiration utilize 1D nanoscale arrays of densely packed cytochromes containing the molecule heme. The assemblies can be mimicked with 1D nanoscale fibrils composed of peptide amphiphiles designed to coordinate heme in dense arrays. To create such materials and assemblies, it is critical to understand the assembly process and what controls the various aspects of hierarchical assembly. MD simulations suggest that shorter alkyl chains on the peptide lead to more dynamic structures than the peptides with longer chains that yield kinetically trapped states. The hydration parameters manifest themselves experimentally through the observation of a dual pH trigger, which controls the peptide assembly rate, the heme binding affinity, and heme organization kinetics. Great strides in understanding the relative complexity of the self-assembly process in relation to incorporating a functional moiety like heme opens up many possibilities in developing abiotic assemblies for bioelectronic devices and assemblies.

Designing 1D multiheme peptide amphiphile assemblies reminiscent of natural systems

“…† [Note: prior to this work, most results were reported in water and the pH was adjusted with ammonium hydroxide to induce self-assembly. The identification of histidine as the pH trigger 13 influenced the decision to work in Tris buffer at pH 8.] In investigations of similar peptides, the kinetics of β-sheet formation were notably slower.…”

“…Through rational design of peptide amphiphiles, 1D nanoscale architectures 12 can be achieved and heme molecules are coordinated to an engineered bis-histidine coordination environment. [13][14][15] The simplicity of the design (alkyl tailbinding site-aliphatic β-sheet-charged head group) makes it possible to explore the sequence space of the peptide in an effort to determine how sequence impacts various properties of the heme molecule. Previous examples have explored varying the coordination environment, the aliphatic beta sheet sequence, the patterning of the sequence, and the length of the alkyl tail.…”

“…Previous examples have explored varying the coordination environment, the aliphatic beta sheet sequence, the patterning of the sequence, and the length of the alkyl tail. [13][14][15] Each of these "tuning knobs" affects the supramolecular organization of the peptide assembly as well as the local coordination and micro-environment surrounding the heme molecule yielding different binding affinities and stoichiometry. Previously, the materials were assembled at high pH values (∼11) to effectively neutralize the charged lysine head group, reducing the electrostatic repulsion between neighboring molecules, thus initiating the assembly of long aspect ratio, β-sheet rich peptide fibers.…”

“…Recently, the peptide c16-AH(KL) 3 -CONH 2 was determined to assemble at pH > 7, just above the p K a of histidine. 13 Essentially, the histidine, when charged, precludes assembly in this particular sequence. Here, the peptides c16-AH(Kx) n (where n = 1–4 and x = L, I, or F and denoted simply as PA-KL1, PA-KL2, etc .…”

A new insight into the push‐pull effect of substituents via the stilbene‐like model compounds

“…Push‐pull effect of substituents is an important concept, which is often employed to improve the properties of organic compounds [1–24], such as UV absorption [4, 15], fluorescence emission [6, 16], intramolecular charge transfer [1, 3, 14], nonlinear optical properties [5, 13], photovoltaic performance [10], organic light‐emitting diode [19], and so on. If we input the word “push‐pull effect” into the Web of Science, we will obtain more than 100,000 items, which implies that the push‐pull effect of substituents is widely used in physics and chemistry.…”