Assessing the Potential of Folded Globular Polyproteins As Hydrogel Building Blocks

Abstract

The native states of proteins generally have stable well-defined folded structures endowing these biomolecules with specific functionality and molecular recognition abilities. Here we explore the potential of using folded globular polyproteins as building blocks for hydrogels. Photochemically cross-linked hydrogels were produced from polyproteins containing either five domains of I27 ((I27)5), protein L ((pL)5), or a 1:1 blend of these proteins. SAXS analysis showed that (I27)5 exists as a single rod-like structure, while (pL)5 shows signatures of self-aggregation in solution. SANS measurements showed that both polyprotein hydrogels have a similar nanoscopic structure, with protein L hydrogels being formed from smaller and more compact clusters. The polyprotein hydrogels showed small energy dissipation in a load/unload cycle, which significantly increased when the hydrogels were formed in the unfolded state. This study demonstrates the use of folded proteins as building blocks in hydrogels, and highlights the potential versatility that can be offered in tuning the mechanical, structural, and functional properties of polyproteins.

The hierarchical emergence of worm-like chain behaviour from globular domain polymer chains

“…Of current interest in the study of these types of polymeric object is their rational design, namely, how we can design polymeric structures with specific and predictable biophysical properties. These may be the end products in and of themselves, such as elastomeric polyproteins 9 or renewable biopolymers 10 , or they may be required for subsequent use in the rational design of more complex systems, such as biopolymer solutions 11 and networks 12,13 , protein hydrogels 14,15 and even mimicking complex biological systems such as cilia and flagella 8 . In each of these applications, both experimental and simulation studies have shown that the microscopic mechanical properties of these polymeric objects have a significant effect on the resulting hierarchical properties, whether it is macroscopic elasticity or network connectivity.…”

“…Yet we have seen from the work of Li et al that in the absence of applied tensile force, the persistence length can be significantly larger. Biophysical systems which incorporate these types of polymeric object as a structural subunit are currently being investigated 14,15,43 , and within these systems it is likely that the subunits are under conditions similar to SMFS experiments. In addition, current theoretical models for the viscoelastic properties of homogeneous semiflexible polymers in solution have recently been shown to be insuffucient 11,12 .…”

High-Strength Albumin Hydrogels With Hybrid Cross-Linking

“…BSA CC gel and BSA DC gel were red-brown ( Figure 1B), indicating the formation of dityrosine bonds after photoreaction. The gelation mechanism of tyrosine-rich protein via APS/Ru(II) under white light is well-known and is illustrated in Figure 1A (Partlow et al, 2016;Silva et al, 2017). Interestingly, different from BSA PC gel, which had an opaque milk-white color, BSA CC gel and BSA DC gel showed high transparency, and the logo of our university could be clearly seen through them ( Figure 1B).…”

“…Because of excellent biocompatibility, natural protein hydrogels have attracted a great deal of attention and have been used in a wide range of biological and biomedical fields (Koetting et al, 2016;Partlow et al, 2016;Silva et al, 2017;Jo et al, 2018;Gacanin et al, 2019). However, the poor mechanical properties of natural protein hydrogels is one of the main drawbacks impeding their application in some cases (Silva et al, 2017;Tang et al, 2018).…”

“…Because of excellent biocompatibility, natural protein hydrogels have attracted a great deal of attention and have been used in a wide range of biological and biomedical fields (Koetting et al, 2016;Partlow et al, 2016;Silva et al, 2017;Jo et al, 2018;Gacanin et al, 2019). However, the poor mechanical properties of natural protein hydrogels is one of the main drawbacks impeding their application in some cases (Silva et al, 2017;Tang et al, 2018). Recently, great efforts have been made to enhance the mechanical properties of natural protein hydrogels, and some strategies have been developed, including nanocomposite (Yuk et al, 2016;Qin et al, 2017;Wang et al, 2017Wang et al, , 2018, physical cross-linking (Toivonen et al, 2015;Feng et al, 2018;Yan et al, 2019;Zhang et al, 2019), solvent induction (Li et al, 2016;Zhang et al, 2016;Hashemnejad et al, 2017;Zhu et al, 2018), double network (Bhattacharjee et al, 2015;Luo et al, 2016;Rangel-Argote et al, 2018;Tavsanli and Okay, 2019), hybrid cross-linking (Moura et al, 2011;Epstein-Barash et al, 2012;Xu et al, 2016;Nojima and Iyoda, 2018;Yang et al, 2018), and so on.…”