Structural Insights into the Mechanism of Heat‐Set Gel Formation of Polyisocyanopeptide Polymers

Abstract

One of the key factors influencing the mechanical properties of natural and synthetic extracellular matrices (ECM) is how large‐scale 3D gel‐like structures emerge from the molecular self‐assembly of individual polymers. Here, structural characterization using small‐angle neutron scattering (SANS) of ECM‐mimicking polyisocyanopeptide (PIC) hydrogels are reported as a function of background ions across the Hofmeister series. More specifically, the process of polymer assembly is examined by probing the structural features of the heat‐set gels and correlating them with their rheological and micro‐mechanical properties. The molecular parameters obtained from SANS clearly show changes in polymer conformation which map onto the temperature‐induced changes in rheological and micro‐mechanical behavior. The formation of larger structures are linked to the formation of cross‐links (or bundles), whilst the onset of their detection in the SANS is putatively linked to their concentration in the gel. These insights provide support for the ‘hot‐spot’ gelation mechanism of PIC heat‐set gels. Finally, it is found that formation of cross‐links and heat‐set gelling properties can be strongly influenced by ions in accordance with Hofmeister series. In practice, these results have significance since ions are inherently present in high concentration during cell culture studies; this may therefore influence the structure of synthetic ECM networks.

Study on the gelation and sustained release effect of the thermosensitive material TPGS1000

“…According to the previous study, 24 monovalent anion salts, such as NaCl and NaH 2 PO 4 could not induce the formation of hydrogel, and cations had no effect on the hydrogelation. Generally, the effect of ions on the gelation roughly followed the Hofmeister series: CO 3 2− > SO 4 2− > S 2 O 3 2− > H 2 PO 4 − > F − > Cl − > Br − ~ NO 3 − > I − > SCN − 36–38 . Therefore, we investigated the effect of Na 2 SO 3 on the gelation of TPGS 1000 .…”

“…According to the previous study, 24 monovalent anion salts, such as NaCl and NaH 2 PO 4 could not induce the formation of hydrogel, and cations had no effect on the hydrogelation. Generally, the effect of ions on the gelation roughly followed the Hofmeister series: [36][37][38] Therefore, we investigated the effect of Na 2 SO 3 on the gelation of TPGS 1000 . It could be found that TPGS 1000 easily formed gel with a translucent status under the condition of 4.5% Na 2 SO 3 (Table 1).…”

Introducing Dihedral Angle Torsion in a Flexible Dicarboxylic Acid: Evolution from a Sequential Symmetry Condensing Liquid Crystalline Gel to a Step-Halting Heat-Set Gel

“…In addition to organic salts, heat-set gelation can also be exhibited by coordination polymers, , organic/biological polymers, − inorganic complexes, and charge transfer complexes . None of these compounds melt or dissolve under conditions conducive to heat-set gelling.…”

“…Heat-set gelators can also be designed by introducing long chains into coordination polymers . Biological polymer materials such as globular protein gel, polyisocyanopeptide polymers, quinoa protein, RuBisCO, konjac glucomannan, and polyurethane/PEG block copolymers can also form heat-set gels. − …”

Hydrogels to engineer tumor microenvironmentsin vitro

“…In recent years, there has been an increased interest in polyisocyanide-based hydrogels for 3D cell culture due its stressinduced stiffening properties, collagen-like helical architecture and thermosensitive properties which allow for facile recovery of encapsulated cells. [277][278][279] Zhang et al developed a polyisocyanide-based hydrogel decorated with the adhesive RGD peptide to form mammary gland organoids. Not only did the hydrogels enable mammary gland organoid formation, the resulting organoids could be maintained for prolonged durations in vitro and retain their ability to branch.…”