Rationally designed synthetic protein hydrogels with predictable mechanical properties

Abstract

Designing synthetic protein hydrogels with tailored mechanical properties similar to naturally occurring tissues is an eternal pursuit in tissue engineering and stem cell and cancer research. However, it remains challenging to correlate the mechanical properties of protein hydrogels with the nanomechanics of individual building blocks. Here we use single-molecule force spectroscopy, protein engineering and theoretical modeling to prove that the mechanical properties of protein hydrogels are predictable based on the mechanical hierarchy of the cross-linkers and the load-bearing modules at the molecular level. These findings provide a framework for rationally designing protein hydrogels with independently tunable elasticity, extensibility, toughness and self-healing. Using this principle, we demonstrate the engineering of self-healable muscle-mimicking hydrogels that can significantly dissipate energy through protein unfolding. We expect that this principle can be generalized for the construction of protein hydrogels with customized mechanical properties for biomedical applications.

Boron Nitride Aerogels with Super‐Flexibility Ranging from Liquid Nitrogen Temperature to 1000 °C

“…Furthermore, 50 cycles of consecutive loading–unloading (Figure c, ε = 40%) exhibited similar features as other superelastic materials, such as graphene foams, CNT aerogels, and silicone aerogels 1f,8. For the recovery process, unrecoverable residual deformations of about ε = 2.8%, ε = 7.6% remained after 10‐ and 50‐cycles at 40% strain, respectively (for more details see Figure S31, Supporting Information) due to the appearance of nanoribbon slippage and fractured junction nodes during the loading–unloading cycles (Figure S28, Supporting Information). The unrecoverable residual deformation is smaller than that of BN microfiber foam6a and comparable to that of superelastic BN nanotubular cellular‐network architectures 6b…”

Chemical unfolding of protein domains induces shape change in programmed protein hydrogels

“…(i) Protein hydrogels typically show weak mechanical integrity and increasing the number of cross-linking sites can improve their stiffness, but at the expense of a narrower tunability 14,27 . 18 For BSA, the minimum gelation concentration is ~0.7 mM, while the saturation concentration is ~4 mM, which translated into a Young's moduli range between 2.5 to 15 kPa 15 . When treated with PEI, BSAbased hydrogels (2 mM) showed a significant increasein the Young's modulus, up to ~65 kPa (~ 6-fold increase), and a wide range of stiffness tunability, ranging from 10 to 60 kPa ( Figure 2).…”

“…It has been challenging to obtain the same smart behavior as that of polymer-based hydrogels, in part due to the limited range where solvents, temperatures and concentrations can be used. Proteins generally require water-based solvents, a narrow salt and pH range, and the working temperature to obtain biomaterials cannot exceed values well above 37 o C. Furthermore, the range of concentrations that can be used to obtain hydrogels is narrow 14,16,18 . At the lower end, a too low protein concentration leads to incomplete network formation, and soft gels with irreversible deformations under strain, due to incomplete cross-linking.…”

“…At the upper end, while the final stiffness of protein-hydrogels can be improved with increasing protein concentration, and hence the cross-linking density, a major limitation comes from the maximum protein solubility. For example, hydrogels made from protein G, domain B1 (GB1), from SH3 or from chimera GB1-HP67 had a minimum gelation concentration of ~150 mg/mL and reached their solubility limit at ~180 mg/mL (which corresponds to ~1.3 to 3.2 mM) 18 . In this concentration range, the gels had a narrow range of stiffness, of ±0.6 kPa to ±3 kPa.…”

Fabrication of three-dimensional proteinaceous micro- and nano-structures by femtosecond laser cross-linking

“…Cell-laden cross-linking using a photoinitiator in conjunction with UV exposure can lead to cytotoxicity, while physical cross-linking results in lower mechanical stability compared to a covalently bonded hydrogel 4 . Nevertheless, because the cross-linking density, resulting mechanical properties and applicable residues are all well controlled by these methods, microfluidic mixers 7,8 , drug delivery colloids 9 and rare element mining 10 are promising applications, in addition to cell culturing for tissue engineering and regenerative medicine 4,8 . These techniques can produce large quantities of structures at reasonable speeds, although it is challenging to establish suitable microenvironments for biological studies.…”