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

Abstract

Programmable behavior combined with tailored stiffness and tunable biomechanical response are key requirements for developing successful materials. However, these properties are still an elusive goal for protein-based biomaterials. Here, we present a new method based on protein-polymer interactions, to manipulate the stiffness of protein-based hydrogels made from bovine serum albumin (BSA) by using polyelectrolytes such as poly(Ethelene)imine (PEI) and poly-L-lysine (PLL) at various concentrations. This approach confers protein-hydrogels tunable wide-range stiffness, from ~ 10 - 60 kPa when treated with PEI, without affecting the protein mechanics and nanostructure. We ascribe the increase in stiffness to the synergistic effect of the non-covalent electrostatic polymer-protein interaction, as well as the polymer-shell that stabilizes the protein domains nanomechanics. We use the 6-fold increase in stiffness induced by PEI to program BSA-hydrogels in various shapes. By utilizing the characteristic protein unfolding we can induce reversible shape-memory behavior of these composite materials using chemical denaturing solutions. We anticipate this novel approach based on protein engineering and polymer reinforcing will enable the development and investigation of new smart biomaterials and extend protein hydrogel capabilities beyond their conventional applications.

Cation-induced shape programming and morphing in protein-based hydrogels

“…S2). These values are comparable with those measured for BSA hydrogels programmed with polyethylenimine (19) and with other polymeric materials using double network or polymer-ion interactions (37). As shown in Fig.…”

“…Recently, we have introduced a new method to obtain shape memory in protein-based hydrogels by stiffening them through adsorbed polyelectrolytes (19). Our approach relies on producing protein hydrogels from bovine serum albumin (BSA), which is homologous to human serum albumin, the most abundant protein in blood plasma.…”

“…Below 1 mM, BSA hydrogels show irreversible plastic deformation under force, indicative of incomplete cross-linking (17). Because of the overall charge of BSA, these protein hydrogels have been programmed by stiffening, induced by the secondary network made from positively charged polyelectrolytes (19). The shape change was induced in this case via the unfolding response of the protein domains in chemical denaturants with complete recovery upon removal of the denaturing solution.…”

Electro-assembly of a dynamically adaptive molten fibril state for collagen

“…4H) again shows the high modulus stimulus sensitivity of the molten fibril state network to (NH 4 ) 2 SO 4 treatment is considerably larger than the modulus stimulus sensitivity of static fiber state network and other protein networks to external stimuli used to adjust noncovalent interaction mechanisms (e.g., Hofmeister salt, metal ions, and temperature). References summarized in table S3 and the Supplementary Materials (41)(42)(43)(44)(45)(46)(47)(48). In summary, Fig.…”

Supramolecular Semi-convertible Hydrogel Enabled Self-Healing Responsive Lubrication Under Dynamic Shearing

“…Smart hydrogels inspired from natural principles and structures have been widely utilized in arti cial joint or tissue [1][2][3][4][5][6] , drug release carrier [7][8][9] , shape memory material [10][11][12] , actuators [13][14][15] and sensors [16,17] . For example, inspired by biological metabolism of living muscle self-growing hydrogel was fabricated for soft robots and intelligent devices; [18] by mimicing the dynamic lubricating mechanism of articular cartilage, a shear-responsive supramolecular lubricating hydrogel was fabricated for cartilage substitution.…”