Exploring the Potential of Benzene-1,3,5-tricarboxamide Supramolecular Polymers as Biomaterials

Abstract

The fast dynamics occurring in natural processes increases the difficulty of creating biomaterials capable of mimicking Nature. Within synthetic biomaterials, water-soluble supramolecular polymers show great potential in mimicking the dynamic behavior of these natural processes. In particular, benzene-1,3,5-tricaboxamide (BTA)-based supramolecular polymers have shown to be highly dynamic through the exchange of monomers within and between fibers, but their suitability as biomaterials has not been yet explored. Herein we systematically study the interactions of BTA supramolecular polymers bearing either tetraethylene glycol or mannose units at the periphery with different biological entities. When BTA fibers were incubated with bovine serum albumin (BSA), the protein conformation was only affected by the fibers containing tetraethylene glycol at the periphery (BTA-OEG 4 ). Coarse-grained molecular simulations showed that BSA interacted with BTA-OEG 4 fibers rather than with BTA-OEG 4 monomers that are present in solution or that may exchange out of the fibers. Microscopy studies revealed that, in the presence of BSA, BTA-OEG 4 retained their fiber conformation although their length was slightly shortened. When further incubated with fetal bovine serum (FBS), both long and short fibers were visualized in solution. Nevertheless, in the hydrogel state, the rheological properties were remarkably preserved. Further studies on the cellular compatibility of all the BTA assemblies and mixtures thereof were performed in four different cell lines. A low cytotoxic effect at most concentrations was observed, confirming the suitability of utilizing functional BTA supramolecular polymers as dynamic biomaterials.

The Martini Model in Materials Science

“…An important example are 1,3,5‐benzenetricarboxamide (BTA)‐based supramolecular polymers, synthetic supramolecular materials which have been studied in detail by Bochicchio, Pavan, and co‐workers. [ 257–263 ] Two Martini models for the BTA core were developed, both capturing the step‐wise cooperative polymerization mechanism which leads to the formation of supramolecular fibers ( Figure ) [ 257 ] : BTA monomers initially aggregate quickly in water due to hydrophobic interactions; the disordered aggregates formed then reorganize into directional oligomers on a slower time scale; such ordered oligomers then fuse to form and elongate the supramolecular fiber on an even slower time scale. In the more refined model, additional charged particles were introduced to improve the stacking interactions between the BTA cores, [ 257 ] similarly to the ones introduced within amino acid side chains by de Jong et al.…”

Desymmetrization via Activated Esters Enables Rapid Synthesis of Multifunctional Benzene-1,3,5-tricarboxamides and Creation of Supramolecular Hydrogelators

“… 10 Additionally, the BTA core offers the ability to connect different side-arms and different BTA monomers (with various functionality) can be mixed to rapidly create libraries of multicomponent materials with tunable fibril structure, dynamics, and mechanical properteis. 10 , 18 , 5 , 19 , 17 This modularity, fibril structure, and potential for multifunctionality make BTAs ideal candidates for biomaterials, 11 especially toward 3D cell culture and tissue engineering applications.…”

Columnar Aggregates of Azobenzene Stars: Exploring Intermolecular Interactions, Structure, and Stability in Atomistic Simulations

“…Such structures are utilized, for instance, in gels [7] and sensing devices [8]. Relatively little-exploited but very promising is the usage of supramolecular systems as adhesives [6,9], in medical and drug delivery applications [6,10], as synthetic biomaterials [11], and in devices to probe or manipulate biological systems [3,12].…”

“…BTAs are used to synthesize supramolecular polymers [21,22], act as gelating agents [23,24], and are employed in different medical applications [25,26]. Moreover, these molecules have promising applications as organic ferroelectric materials, e.g., for memory devices [27], and for the design of synthetic biopolymers [11].…”