Self-assembling peptides are a category of peptides which undergo spontaneous assembling into ordered nanostructures. These designer peptides have attracted huge interest in the field of nanotechnology for its potential for application in areas such as biomedical nanotechnology, cell culturing, molecular electronics, and more.
Effectively they act as building blocks for a wide range of material and device applications. The essence of this technology is to replicate what nature does: to use molecular recognition processes to form ordered assemblies of building blocks that are capable of conducting biochemical activities.
Production / Synthesis
Peptide synthesis can be easily conducted by the established method of solid-phase chemistry in grams or kilograms quantities. The d-isomer conformation can be used for peptide synthesis.
Nanostructures can be made by dissolving dipeptides in 1,1,1,3,3, 3-hexafluoro-2-propanol at 100 mg/ml and then diluting it with water for a concentration of less than 2 mg/ml. Multiwall nanotubes with a diameter of 80–300 nm, made of dipeptides from the diphenylalanine motif of Alzheimer’s β-amyloid peptide is made by this method(If a thiol is introduced into the diphenylalanine then nano-spheres can be formed instead; nanospheres of 10–100 nm diameter from a diphenylgalcine peptide can also be made this way.
Dynamic light scattering studies show structures of surfactant peptides.Surfactnt peptides has been studied using a quick-freeze /deep–etch sample preparation method which minimizes effects on the structure. The sample nanostructures are flash freeze at −196 °C and can be studied three dimensionally. Transmission electron microscopy was used.
Structure
Moreover, so far most of the peptide structures formed are in 1 or 2-D , whereas in nature most biological structures are in 3D.Critique has been made in light of the fact that there is a lack in theoretical knowledge about the self-assembling behaviours of peptides. This knowledge could prove to be very useful in facilitating rational designs and precise control of the peptide assemblies. Lastly, although an extensive amount of work is being conducted on developing self-assembling peptide related applications, issues such as commercial viability and processability has not been paid the same amount of attention. Yet it is crucial for these issues to be assessed if the applications were to be realized.
Effectively they act as building blocks for a wide range of material and device applications. The essence of this technology is to replicate what nature does: to use molecular recognition processes to form ordered assemblies of building blocks that are capable of conducting biochemical activities.
Production / Synthesis
Nanostructures can be made by dissolving dipeptides in 1,1,1,3,3, 3-hexafluoro-2-propanol at 100 mg/ml and then diluting it with water for a concentration of less than 2 mg/ml. Multiwall nanotubes with a diameter of 80–300 nm, made of dipeptides from the diphenylalanine motif of Alzheimer’s β-amyloid peptide is made by this method(If a thiol is introduced into the diphenylalanine then nano-spheres can be formed instead; nanospheres of 10–100 nm diameter from a diphenylgalcine peptide can also be made this way.
Characterization
Atomic force microscopy can measure mechanical properties of nanotubes. Scanning electron and atomic forces microscopy is used to examine Lego peptide nanofiber structures.
Dynamic light scattering studies show structures of surfactant peptides.Surfactnt peptides has been studied using a quick-freeze /deep–etch sample preparation method which minimizes effects on the structure. The sample nanostructures are flash freeze at −196 °C and can be studied three dimensionally. Transmission electron microscopy was used.Structure
Dipeptides
The simplest peptide building blocks are dipeptides. Nanotubes formed from dipeptides are the widest amongst peptide nanotubes. An example of a dipeptide that has been studied is such a peptide is one from the diphenylalanine motif of the Alzheimer’s β-amyloid peptide.
Ionic self-complementary pepetides
They are approximately 5 nm in size and has 16 amino acids. The class of Lego peptides has the unique characteristics of having two distinct surfaces being either hydrophobic or hydrophilic, similar to the pegs and holes of Lego blocks.The hydrophobic side promotes the self assemblying process in water and the hydrophilic sides has a regular arrangement of charged amino acids residues, which in turn brings about a defined pattern of ionic bonds. The arrangement of the residues can be classified according to the order of the charges; Modulus I has a charge pattern of “+-+-+-,” modulus II “++--++--“ and modulus III “+++---+++” and so on. The peptides self assemble into nano fibers approximately 10 nm long in the presence of alkaline cations or an addition of peptide solution. The fibers forms ionic interactions with each other to form checkerboard like matrices, which develops into a scafford hydrogel with a high water content of larger than 99.5- 99.9% and pores of 10-200 nm diameter. These hydrogels allows neurite outgrowth and therefore is can be used as scafford for tissue engineering.
Surfactant peptides
Surfactant –like peptides which undergoes self assembly in water to form nanotubes and noanovesicles has been designed using natural lipids as a guide. This class of peptides has a hydrophilic head (with one or two charged amino acids such as aspartic and glutamic acids, or lysine or histidine acids) with a hydrophobic tail (with 4 or more hydrophobic amino acids such as alanine, valine or leucine). The peptide monomers are about 2-3 nm long and consist of seven or eight amino acids; the length of the peptide can be adjusted by adding or removing acid acids.
In water surfactant peptides undergo self assembling to form well ordered nanotubes and nanovesicles of 30–50 nm through intermolecular hydrogen bonds and the packing of the hydrophobic tails in between the residues in a manner similar to micelle formation.Transmission electron microscopy examination on quick-freezed samples of surfactant peptides structures showed helical open-ended nanotubes. The samples also showed a dynamic behaviours and some vesicles “buds” out of the peptide nanotubes.
Carpet peptides
This class of peptides are undergoes self assemblying on a surface and form monolayers just few nanometers thick. This type of molecular “paint” or “carpet” peptides are able to form cell patterns, interact with or trap other molecules onto the surface.This class of peptides consists of three segments: the head is a ligand part which has functional groups attached for recognition by other molecules or cell surface receptors; the middle segment is a “linker”which allows the head to interact at a distance away from the surface.The linker also controls the flexibility and the rigidity of the peptide structure.On the other end of the linker was a surface anchor where a chemical group on the peptide forms a covalent bond with a particular surface.
MOLECULAR ‘SWITCH’ PEPTIDES
This class of peptides has the unique property of being able to change their molecular structure dramatically.This property is best illustrated using an example. The DAR16-IV peptide, has 16 amino acid and forms a 5 nm β-sheet structure at ambient temperatures; a swift change in structure occurs at high temperature or a change in pH and a 2.5 nm α-helix forms.
Cyclic peptides
Extensive research has been performed on nanotubes formed by stacking cyclic peptides with an even number of alternating D and L amino acids. These nanotubes are the narrowest formed by peptides. The stacking occurs through intermolecular hydrogen bonding and the end product is cylindrical structures with the amino acid side chains of the peptide defining the properties of the outer surface of the tube and the peptide backbone determining the properties of the inner surface of the tube. Polymers can also be covalently attached to the peptides in which case a polymer shell around nanotubes can be formed. By applying peptide design, the inner diameter, which is completely uniform, can be specified; the outer surface properties can also be deliberated by peptide design and therefore these cyclic nanotubes are able to form in range of different environments.
Self-assembling peptides versus carbon nanotubes
Carbon nanotubes (CNTs) is another type of nanomaterial which has attracted a lot of interest for its potential as being building blocks for bottom-up applications. They have excellent mechanical, electrical,and thermal properties and can be fabricated to a wide range of nanoscale diameters, making them attractive and appropriate for the developments of electronic and mechanical devices.They demonstrate metal-like properties and are able to act as remarkable conductors. However, there are several areas where peptides has advantages over CNTs. As mentioned in the background section, one advantage that peptides has over carbon as nanosize building blocks is that they have almost limitless chemical functionality compared with the very chemical interactions that carbons can perform due to their nonreactiveness.Furthermore, CNTs exhibits strong hydrophobicity which results in a tendency to clump in aqueous solutions and therefore has limited solubility; their electrical properties are also affected by humidity, and the presence of oxygen, N2O and NH3.It is also difficult for to produce CNTs with uniform properties and this pose serous drawbacks as for commercial purposes the reproducibility of precise structural properties is a key concern. Lastly, CNTs are expensive with prices in the range of hundreds of dollars per gram, rendering most applications of them commercially unviable.
Applications
Cell culturing
Biomedical applications
Molecular electronics applications
Limitations
Although well ordered nanostructures have already been successfully formed from self-assembling peptides, their potential will not be fully fulfilled until useful functionality is incorporated into the structures. These functionalities could include bio-recognition, enzymatic activities into
Moreover, so far most of the peptide structures formed are in 1 or 2-D , whereas in nature most biological structures are in 3D.Critique has been made in light of the fact that there is a lack in theoretical knowledge about the self-assembling behaviours of peptides. This knowledge could prove to be very useful in facilitating rational designs and precise control of the peptide assemblies. Lastly, although an extensive amount of work is being conducted on developing self-assembling peptide related applications, issues such as commercial viability and processability has not been paid the same amount of attention. Yet it is crucial for these issues to be assessed if the applications were to be realized.
