Complex Coacervate Core Micelles with Spectroscopic Labels for Diffusometric Probing of Biopolymer Networks

Abstract

We present the design, preparation, and characterization of two types of complex coacervate core micelles (C3Ms) with cross-linked cores and spectroscopic labels and demonstrate their use as diffusional probes to investigate the microstructure of percolating biopolymer networks. The first type consists of poly(allylamine hydrochloride) (PAH) and poly(ethylene oxide)-poly(methacrylic acid) (PEO-b-PMAA), labeled with ATTO 488 fluorescent dyes. We show that the size of these probes can be tuned by choosing the length of the PEO-PMAA chains. ATTO 488-labeled PEO113-PMAA15 micelles are very bright with 18 dye molecules incorporated into their cores. The second type is a (19)F-labeled micelle, for which we used PAH and a (19)F-labeled diblock copolymer tailor-made from poly(ethylene oxide)-poly(acrylic acid) (mPEO79-b-PAA14). These micelles contain approximately 4 wt % of (19)F and can be detected by (19)F NMR. The (19)F labels are placed at the end of a small spacer to allow for the necessary rotational mobility. We used these ATTO- and (19)F-labeled micelles to probe the microstructures of a transient gel (xanthan gum) and a cross-linked, heterogeneous gel (κ-carrageenan). For the transient gel, sensitive optical diffusometry methods, including fluorescence correlation spectroscopy, fluorescence recovery after photobleaching, and super-resolution single nanoparticle tracking, allowed us to measure the diffusion coefficient in networks with increasing density. From these measurements, we determined the diameters of the constituent xanthan fibers. In the heterogeneous κ-carrageenan gels, bimodal nanoparticle diffusion was observed, which is a signpost of microstructural heterogeneity of the network.

Complex coacervate‐based materials for biomedicine

“…2,4,7,8,[16][17][18]33,35,36,38,72,73,110,117,180,191 Coacervation-based encapsulation has been widely used in food science, medicine, sensing, and in the development of nanoreactors. 19,27,57,59,77,107,108,110,114,115,[192][193][194][195][196][197][198][199] Encapsulation can be achieved by utilizing the cargo material as part of the coacervate matrix, 4,8,15,72,81,128,136,137,140,146,[200][201][202][203] as a result of specific interactions, 115 or by preferential partitioning. 4,…”

“…The welldefined size and aggregation number of coacervatecore micelles have facilitated their use as fluorescent nanoprobes for the characterization of diffusive behavior in fluorescence recovery after photobleaching (FRAP) studies. 192,193 However, an important consideration in the development of such diffusional probes is the effect of environmental changes on the size and stability of the particle. One possibility for stabilizing such particles is through a crosslinking reaction, such as the amidation reaction that can occur at high temperatures between a carboxylate and an amine.…”

On Complex Coacervate Core Micelles: Structure-Function Perspectives

“…Exciting emerging applications of C3Ms also profit from the uniquely responsive nature of C3Ms and advances in controlled polymerization techniques, which enable the preparation of micelles with increasingly custom-tailored structure, stability, properties, and function. The incorporation of multivalent metal ions, spectroscopic probes, multiblock copolymers, stimuli-responsive (macro)molecules or nanoparticles, and unconventional water-soluble blocks extends the functionality of C3Ms to, e.g., diffusional probes [ 168 , 169 ], contrast agents and imaging probes [ 138 , 170 , 171 , 172 , 173 ], nanoreactors [ 174 ], hydrogelators [ 175 ], and crystal growth modifiers [ 176 ], and facilitates in-depth characterization at the ensemble and single-micelle level [ 177 , 178 , 179 ]. The straightforward preparation by direct dissolution from cost-effective raw materials further facilitates the translation of key concepts and innovations with high application potential into marketable technologies.…”

Estimating microstructural length scales in κ-carrageenan hydrogels by PFG NMR nanoprobe diffusometry

“…Particles larger than the structural features of the polymer network are completely immobilized. [2][3][4] The latter effect has been observed in polysaccharide hydrogels if the size of the particles exceeds a certain threshold, which likely corresponds to the size of the smallest interstitials between the polymer strands. 5 For the largest part, however, diffusion of nanoparticles remains hindered but unrestricted.…”