Peptide amphiphile

Peptide amphiphiles are peptide-based molecules that self-assemble into structures including high aspect ratio nanofibers. A peptide amphiphile typically comprises a hydrophilic peptide sequence with an attached lipid chains, in this case being a lipopeptide. They were first described by the group of Matthew Tirrell in 1995. These molecules are often composed of multiple domains which allow self-assembly into various supramolecular structures. The individual domains associate with each other and result in growth of larger assemblies. Work by Hartgerink et al. in the early 2000s demonstrated a peptide amphiphile which has three regions: a hydrophobic tail, a region of beta-sheet forming amino acids, and a peptide epitope designed to allow solubility of the molecule in water, perform a biological function by interacting with living systems, or both. Self-assembly occurs by the combination of hydrogen-bonding between beta-sheet forming amino acids and hydrophobic collapse of the tails to yield the formation of cylindrical micelles that present the peptide epitope at extremely high density at the nanofiber surface. In a newer system developed by Hartgerink in the mid 2000s, multidomain peptides consisting nominally of alternating hydrophobic and hydrophilic amino acids, with terminal lysines self-assemble into parallel or anti-parallel beta sheets. This self-assembly of molecules into fibers occurs spontaneously in all solutions of peptide amphiphiles, which have a vanishingly small critical micelle concentration. By changing pH or adding counterions to screen the charged surfaces of fibers, gels can be formed. It has been shown that injection of peptide amphiphile solutions in vivo leads to in situ gel formation due to the presence of counterions in physiological solutions. This, along with the complete biodegradability of the materials, suggests numerous applications in in vitro and in vivo therapies. Peptide amphiphiles are peptide-based molecules that self-assemble into structures including high aspect ratio nanofibers. A peptide amphiphile typically comprises a hydrophilic peptide sequence with an attached lipid chains, in this case being a lipopeptide. They were first described by the group of Matthew Tirrell in 1995. These molecules are often composed of multiple domains which allow self-assembly into various supramolecular structures. The individual domains associate with each other and result in growth of larger assemblies. Work by Hartgerink et al. in the early 2000s demonstrated a peptide amphiphile which has three regions: a hydrophobic tail, a region of beta-sheet forming amino acids, and a peptide epitope designed to allow solubility of the molecule in water, perform a biological function by interacting with living systems, or both. Self-assembly occurs by the combination of hydrogen-bonding between beta-sheet forming amino acids and hydrophobic collapse of the tails to yield the formation of cylindrical micelles that present the peptide epitope at extremely high density at the nanofiber surface. In a newer system developed by Hartgerink in the mid 2000s, multidomain peptides consisting nominally of alternating hydrophobic and hydrophilic amino acids, with terminal lysines self-assemble into parallel or anti-parallel beta sheets. This self-assembly of molecules into fibers occurs spontaneously in all solutions of peptide amphiphiles, which have a vanishingly small critical micelle concentration. By changing pH or adding counterions to screen the charged surfaces of fibers, gels can be formed. It has been shown that injection of peptide amphiphile solutions in vivo leads to in situ gel formation due to the presence of counterions in physiological solutions. This, along with the complete biodegradability of the materials, suggests numerous applications in in vitro and in vivo therapies. The modular nature of the chemistry allows the tuning of both the mechanical properties and bioactivities of the resulting self-assembled fibers and gels. Bioactive sequences can be used to bind growth factors to localize and present them at high densities to cells, or to directly mimic the function of endogenous biomolecules. Epitopes mimicking the adhesive RGD loop in fibronectin, the IKVAV sequence in laminin and a consensus sequence to bind heparin sulfate are just a few of the large library of sequences that have been synthesized. These molecules and the materials made from them have been shown to be effective in promoting cell adhesion, wound healing, mineralization of bone, differentiation of cells and even recovery of function after spinal cord injury in mice. In addition to this, peptide amphiphiles can be used to form more sophisticated architectures which can be tuned on demand. In recent years, two discoveries have yielded bioactive materials with more advanced structures and potential applications. In one study, a thermal treatment of peptide amphiphile solutions led to the formation of large birefringent domains in the material that could be aligned by a weak shear force into one continuous monodomain gel of aligned nanofibers. The low shear forces used in aligning the material permit the encapsulation of living cells inside these aligned gels and suggest several applications in regenerating tissues that rely on cell polarity and alignment for function. In another study, the combination of positively charged peptide amphiphiles and negatively charged long biopolymers led to the formation of hierarchically ordered membranes. When the two solutions are brought into contact, electrostatic complexation between the components of each solution creates a diffusion barrier that prevents the mixing of the solutions. Over time, an osmotic pressure difference drives the reptation of polymer chains through the diffusion barrier into the peptide amphiphile compartment, leading to the formation of fibers perpendicular to the interface that grow over time. These materials can be made in the form of flat membranes or as spherical sacs by dropping one solution into the other. These materials are robust enough to handle mechanically and a range of mechanical properties can be accessed by altering growth conditions and time. They can incorporate bioactive peptide amphiphiles, encapsulate cells and biomolecules, and are biocompatible and biodegradable.