Control of Amphiphile Self-Assembly via Bioinspired Metal Ion Coordination

Abstract

Inspired by marine siderophores that exhibit a morphological shift upon metal coordination, hybrid peptide-polymer conjugates that assemble into different morphologies based on the nature of the metal ion coordination have been designed. Coupling of a peptide chelator, hexahistidine, with hydrophobic oligostyrene allows a modular strategy to be established for the efficient synthesis and purification of these tunable amphiphiles (oSt(His)₆). Remarkably, in the presence of different divalent transition metal ions (Mn, Co, Ni, Cu, Zn, and Cd) a variety of morphologies were observed. Zinc(II), cobalt(II), and copper(II) led to aggregated micelles. Nickel(II) and cadmium(II) produced micelles, and multilamellar vesicles were obtained in the presence of manganese(II). This work highlights the significant potential for transition metal ion coordination as a tool for directing the assembly of synthetic nanomaterials.

Figure 1.

Schematic illustrating a single amphiphilic material that can be transformed into a variety of unique morphologies in response to the presence of different divalent transition metal ions.

Figure 2.

Synthesis of maleimide-terminated oligostyrene. (a) Synthetic scheme; (b) ¹H NMR spectrum of the protected-maleimide oligomer demonstrating chain end fidelity.

Figure 3.

(a) Synthetic scheme for the coupling of oligostyrene to hexahistidine peptide via maleimide–cysteine reaction; (b) MALDI MS confirming synthesis of the peptide–polymer amphiphile. The arrow indicates the difference of a single styrene monomer unit.

Figure 4.

Schematic of the oSt(His)₆ and assembled structures in the absence (left) and presence (right) of Zn(II) (15 mM) in addition to cryo-TEM images. Scale bars represent 200 nm (larger image) and 20 nm (inset image).

Figure 5.

Varying concentrations of Zn(II) lead to different degrees of aggregation. Negative-stained TEM images of oSt(His)₆ (600 μM) assembled with 0–15 mM Zn(II). Negative staining was performed with uranium formate, and all scale bars represent 200 nm. All assembly was performed in buffered solution (HEPES, 100 mM, pH 7).

Figure 6.

TEM images of oSt(His)₆ assembled in the presence of Zn(II) with different incubation times and temperatures. Samples negatively stained with uranium formate. All scale bars represent 200 nm.

Figure 7.

Assembly of oSt(His)₆ in the presence of divalent transition metals. Cryo-TEM images show oSt(His)₆ assembled in the presence of Mn(II), multilamellar vesicles; Co(II)/Cu(II), aggregated micelles; and Ni(II)/Cd(II), micelles. Scale bars represent 200 nm (larger image) and 20 nm (inset image).

Figure 8.

Proposed binding modes of oSt(His)₆ to divalent transition metals. (a) Illustration of the proposed coordination of oSt(His)₆ to divalent ions. Number distributions from DLS for oSt(His)₆ assembled in the presence of different numbers of equivalents of (b) Ni(II) and (c)Mn(II).

Scheme 1.

Modular Design Strategy for the Synthesis of oSt(His)₆