Supramolecular Hydrogel Induced by Electrostatic Interactions between Polycation and Phosphorylated-Fmoc-Tripeptide

Abstract

Supramolecular hydrogels formed through non-covalent interactions of low molecular weight hydrogelators (LMWH) show great potential applications in different fields, such as delivery of therapeutics, injectable biomaterials, catalysis or materials chemistry. Generally, the self-assembly of LMWH is triggered by a sol-gel process through an external stimulus able to switch their solubility, such as temperature, pH or solvent change and chemical or enzymatic reactions. In this work, we introduced a new strategy to trigger and control the self-assembly of Fmoc-FFpY peptides: by direct electrostatic interactions with a polycation without dephosphorylation of the peptides. The resulting hydrogels show enhanced mechanical properties in comparison to gels of Fmoc-FFpY induced by enzymatic dephosphorylation. Peptide self-assembly yields -sheets, revealed by circular dichroism and infrared spectroscopy. Characteristic distances predicted by geometry optimization in the gas phase are in agreement with X-ray scattering data and TEM observations. It is proposed that core-shell cylinders are formed in which polycation chains decorate the micellar structures of Fmoc-FFpY peptides through electrostatic interactions between the charged amine groups of the polycations and the phosphate groups of the peptides. Since the gels form quickly and have superior mechanical properties, applications as injectable biomaterials are foreseen. This work opens a route towards a new class of self-assembled hydrogels, where Fmoc tripeptides can be self-assembled with specific polycations to obtain, for example, antimicrobial hydrogels.

Controlling hydrogel properties by tuning non-covalent interactions in a charge complementary multicomponent system

“…The emergence of the new peak at 462 nm validates overlapping of the uorenyl groups at high pH. 20,31,39,40 To conrm this, concentration variable emission spectra of the individual components were recorded. Compound 1 exhibited weak emission in the region 350-500 nm (as broad band) both at acidic and basic pH (Fig.…”

“…14 A well-known method of synthesizing multicomponent gels is to mix two organic compounds bearing pH responsive, oppositely charged functionalities. 10,11,[15][16][17][18][19][20] In these gels, the electrostatic interactions between the positively and negatively charged groups act as the key driving force to build up the underlying network. 12,[20][21][22][23] Additionally, tuning of material properties is possible simply by controlling the surface charge on the bres through pH change.…”

“…10,11,[15][16][17][18][19][20] In these gels, the electrostatic interactions between the positively and negatively charged groups act as the key driving force to build up the underlying network. 12,[20][21][22][23] Additionally, tuning of material properties is possible simply by controlling the surface charge on the bres through pH change. 22 Many natural systems and processes such as assembly of proteins and silk brils involve multicomponent ionic interactions.…”

“…23 In comparison, mixing of two nongelling compounds resulting in the formation of a gel is unusual and challenging. 11,20,[32][33][34][35] For instance, in a recent study, Hu et al demonstrated two co-assembled peptide systems that aggregate to form gels involving electrostatic interactions although none of the components self-assembled into hydrogels by themselves. 36 In this work, we report an unusual pH responsive multicomponent gel network by varying the preparative pathway.…”

Surface Triggered Self-Assembly of Fmoc-Tripeptide as an Antibacterial Coating

“…In the last decade, low molecular weight hydrogelators (LMWH) fabricated from natural biomolecules such as amino acids got great interest due to their ease and powerful bottom-up fabrication. They self-assemble into supramolecular hydrogels by non-covalent interactions, i.e., electrostatic, van der Waals forces, hydrogen bonding and π-π stacking ( McCloskey et al, 2014 ), in response to external stimuli, such as temperature change ( Collier et al, 2001 ), pH switch ( Aggeli et al, 2003 ; Chen et al, 2011 ), solvent change ( Mahler et al, 2006 ), electrostatic interactions ( Criado-Gonzalez et al, 2020b ), chemical ( Bowerman and Nilsson, 2010 ; Zhao et al, 2011 ) or enzymatic reactions ( Yang et al, 2004 ; Yang and Xu, 2006 ; Criado-Gonzalez et al, 2019b ). Ultrashort peptides, up to 7 amino acids in length, are an emerging class of LMWH of increasing interest due to their versatility in molecular design, ease synthesis, and costs reduction.…”