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Synthesis and Characterization of Cationic Hydrogels from Thiolated Copolymers for Independent Manipulation of Mechanical and Chemical Properties of Cell Substrates.

Cells sense both mechanical and chemical properties in their environment and respond to these inputs with altered phenotypes. Precise and selective experimental manipulations of these environmental cues require biocompatible synthetic materials, for which multiple properties can be fine-tuned independently from each other. For example, cells typically show critical thresholds for cell adhesion as a function of substrate parameters such as stiffness and the degree of functionalization. However, the choice of tailor-made, defined materials to produce such cell adhesion substrates is still very limited. Here, we present a platform of synthetic hydrogels based on well-defined thiolated copolymers. Therefore, we have prepared four disulfide crosslinked hydrogels of different composition by free radical polymerisation. After cleavage with dithiothreitol (DTT) four soluble copolymers P1 - P4 with 0 - 96% cationic monomer content were obtained. We then combined P1 and P4 with PEGDA3500 as a crosslinker, to fabricate twelve hydrogels with variable elasticity, ranging from 8.1 - 26.3 kPa and cationic group concentrations of up to 350 μmol/cm3 . Systematic analysis using COS7 cells, showed that all of these hydrogels are non-toxic. However, successful cell adhesion required both a minimal elasticity and a minimal cationic group concentration. This article is protected by copyright. All rights reserved.