Tunable and Large-Scale Model Network StarPEG-DNA Hydrogels

Abstract

The use of DNA as a building block in synthetic polymer hydrogels promises high levels of programmability regarding sol/gel temperatures, tunable bond lifetimes, biocompatibility, and interaction with biological components (e.g., enzymes, cells, and growth factors). However, scalability and quantitative structure−property relationships for large-scale materials are still challenging to achieve. Building on our recently introduced and scalable one-pot liquid-phase oligonucleotide synthesis of DNA onto star-shaped poly(ethylene glycol) (PEG), we here report hydrogels based on starPEG-DNA conjugates together with divalent DNA linkers of tunable duplex hybridization length. By systematically varying parameters such as the duplex melting temperature, salinity, and building block concentrations, we establish the mechanical phase space of such hydrogels. We elucidate tunable mechanical properties ranging from a few Pa to the kPa regime and discuss time scales of self-healing and bond exchange, as well as tunable sol/gel transition temperatures. These comprehensive investigations shed some light on the future design principles for DNA hydrogel materials based on scalable building blocks, that allow for the formation of quasi-ideal networks due to their starshaped and flexible building block topologies. Such materials can be useful in the field of biomedicine and cell culture.

Star‐Polymer–DNA Gels Showing Highly Predictable and Tunable Mechanical Responses

“…Such simple viscoelastic behavior was not observed in the randomly crosslinked DNA gels [26] and the DNA gels with sequences not showing the two-state transition. [20,43] The high homogeneity of the star-polymer-DNA gel and its well-designed DNA sequences showing the two-state transition likely simplified the relaxation behavior of the DNA gels. A characteristic stressrelaxation time, which corresponds to the cross point of the G′ and G″ curves, was more precisely estimated by fitting each curve with the Maxwell model (Figure S11, Supporting Information) and is shown later.…”

“…[ 37,40,41 ] Although a similar strategy was employed for DNA gels, the viscoelastic properties of the DNA gels were still complicated. [ 20,43 ] Moreover, the gel network homogeneity and relation between the DNA sequences and the gel's viscoelastic properties have not yet been investigated.…”

Star polymer networks: a toolbox for cross-linked polymers with controlled structure

“…16): [2 + 2] or [4 + 4] cycloaddition, 6,[253][254][255][256][257][258][259] hydrogen bonding, 260 reverisble Alderene reaction, 261 reversible radical coupling, [262][263][264] peptide coiled coil formation, 265 and DNA hybridization. 266,267 Some π-electron systems undergo cycloaddition (Fig. 16a), the representative of which is the DA reaction ([4 + 2] cycloaddition, section 4.2).…”

“…Tan and coworkers adopted a Watson-Crick base pair, adenine and thymine, as a reversible linkage between star polymers 260 260 (c) reversible Alder-ene reaction, 261 (d) reversible radical coupling, [262][263][264] (e) peptide coiled coil formation, 265 and (f ) DNA hybridization. 266,267…”

“…The same group later applied the strategy to A 2 + B 4 scheme, i.e., hybridization of a linker with two ssDNA moieties and 4f-PEG-ssDNA. 267…”