Shape-Shifting Peptide Nanomaterials: Surface Asymmetry Enables pH-Dependent Formation and Interconversion of Collagen Tubes and Sheets

Abstract

The fabrication of dynamic, transformable biomaterials that respond to environmental cues represents a significant step forward in the development of synthetic materials that rival their highly functional, natural counterparts. Here, we describe the design and synthesis of crystalline supramolecular architectures from charge-complementary heteromeric pairs of collagen-mimetic peptides (CMPs). Under appropriate conditions, CMP pairs spontaneously assemble into either 1D ultraporous (pore diameter > 100 nm) tubes or 2D bilayer nanosheets due to the structural asymmetry that arises from heteromeric self-association. Crystalline collagen tubes represent a heretofore unobserved morphology of this common biomaterial. In-depth structural characterization from a suite of biophysical methods, including TEM, AFM, high-resolution cryo-EM, and SAXS/WAXS measurements, reveals that the sheet and tube assemblies possess a similar underlying lattice structure. The experimental evidence suggests that the tubular structures are a consequence of the self-scrolling of incipient 2D layers of collagen triple helices, and that the scrolling direction determines the formation of two distinct structural isoforms. Furthermore, we show that nanosheets and tubes can spontaneously interconvert through manipulation of the assembly pH and systematic adjustment of the CMP sequence. Altogether, we establish initial guidelines for the construction of dynamically responsive 1D and 2D assemblies that undergo a structurally programmed morphological transition.

Structures of synthetic helical filaments and tubes based on peptide and peptido-mimetic polymers

“…The sheet form was dominant at neutral pH, which suggested that the tubes represented a kinetic product. A similar pH-dependent transition between sheets and scrolled tubes was reported for a series of designed collagen-mimetic peptides (Merg et al ., 2020). These data suggested that preformed supercoiled peptide motifs could serve as protomers for the creation of shape-shifting nanomaterials that could toggle between sheet-like and tubular forms.…”

Bottom-up supramolecular assembly in two dimensions

“…Rigid diblock monomers can also incorporate ionic domains to control directional growth, which allows the ordered assembly of 2D bilayers from flat amphiphilic peptoids 75 and cylindrical coiled-coils. 57 Our group recently reported cyclic d / l -alternating peptides that grow 1D nanotubes via backbone H-bonding, 76 whose hydrophobic face induces their subsequent assembly into 2D bilayers by inter-tubular hydrophobic interactions ( Fig. 2C ).…”

“…56 In certain cases, implementation of comonomers with geometrical restrictions can be used to control the structural fate of the nal assemblies. 57 Frustration of the crystallisation process can also be achieved by monomer composition to obtain complex structures such as toroidal micelles with a tuneable size. 58 Stoppers.…”

Genetically engineered materials: Proteins and beyond

“…These researchers further engineered the intrinsically disordered proteins (IDPs) based on the sequence-property relationship, thus enabling the modulation of phase separation in living cells [80]. Conticello and co-workers [81] created pH-dependent interconversion of collagen tubes and sheets using heteromeric pairs of collagen-mimetic peptides with carefully selected number and position of charged residues for charge complementary. The controllable transformation between different assembly structures and morphologies would be promising in designing versatile and smart carriers of a diverse spectrum of molecular payloads.…”