Self-assembling Peptide Systems Research Articles

Morphoscanner2.0: A new python module for analysis of molecular dynamics simulations.

Molecular dynamics simulations, at different scales, have been exploited for investigating complex mechanisms ruling biologically inspired systems. Nonetheless, with recent advances and unprecedented achievements, the analysis of molecular dynamics simulations requires customized workflows. In 2018, we developed Morphoscanner to retrieve structural relations within self-assembling peptide systems. In particular, we conceived Morphoscanner for tracking the emergence of β-structured domains in self-assembling peptide systems. Here, we introduce Morphoscanner2.0. Morphoscanner2.0 is an object-oriented library for structural and temporal analysis of atomistic and coarse-grained molecular dynamics (CG-MD) simulations written in Python. The library leverages MDAnalysis, PyTorch and NetworkX to perform the pattern recognition of secondary structure patterns, and interfaces with Pandas, Numpy and Matplotlib to make the results accessible to the user. We used Morphoscanner2.0 on both simulation trajectories and protein structures. Because of its dependencies on the MDAnalysis package, Morphoscanner2.0 can read several file formats generated by widely-used molecular simulation packages such as NAMD, Gromacs, OpenMM. Morphoscanner2.0 also includes a routine for tracking the alpha-helix domain formation.

Peptide Self-Assembled Nanocarriers for Cancer Drug Delivery.

The design of novel cancer drug nanocarriers is critical in the framework of cancer therapeutics. Nanomaterials are gaining increased interest as cancer drug delivery systems. Self-assembling peptides constitute an emerging novel class of highly attractive nanomaterials with highly promising applications in drug delivery, as they can be used to facilitate drug release and/or stability while reducing side effects. Here, we provide a perspective on peptide self-assembled nanocarriers for cancer drug delivery and highlight the aspects of metal coordination, structure stabilization, and cyclization, as well as minimalism. We review particular challenges in nanomedicine design criteria and, finally, provide future perspectives on addressing a portion of the challenges via self-assembling peptide systems. We consider that the intrinsic advantages of such systems, along with the increasing progress in computational and experimental approaches for their study and design, could possibly lead to novel classes of single or multicomponent systems incorporating such materials for cancer drug delivery.

Stimulus-Responsive Amino Acids Behind In Situ Assembled Bioactive Peptide Materials.

In situ self-assembly of peptides into well-defined nanostructures represents one of versatile strategies for creation of bioactive materials within living cells with great potential in disease diagnosis and treatment. The intimate relationship between amino acid sequences and the assembling propensity of peptides has been thoroughly elucidated over the past few decades. This has inspired development of various controllable self-assembling peptide systems based on stimuli-responsive naturally occurring or non-canonical amino acids, including redox-, pH-, photo-, enzyme-responsive amino acids. This review attempts to summarize the recent progress achieved in manipulating in situ self-assembly of peptides by controllable reactions occurring to amino acids. We will highlight the systems containing non-canonical amino acids developed in our laboratory during the past few years, primarily including acid/enzyme-responsive 4-aminoproline, redox-responsive (seleno)methionine, and enzyme-responsive 2-nitroimidazolyl alanine. Utilization of the stimuli-responsive assembling systems in creation of bioactive materials will be specifically introduced to emphasize their advantages for addressing the concerns lying in disease theranostics. Eventually, we will provide the perspectives for the further development of stimulus-responsive amino acids and thereby demonstrating their great potential in development of next-generation biomaterials.

Fabrication of lumen-forming colorectal cancer organoids using a newly designed laminin-derived bioink.

160Three-dimensional (3D) bioprinting systems, which are the prominent tools for biofabrication, should evolve around the cutting-edge technologies of tissue engineering. This is the case with organoid technology, which requires a plethora of new materials to evolve, including extracellular matrices with specific mechanical and biochemical properties. For a bioprinting system to facilitate organoid growth, it must be able to recreate an organ-like environment within the 3D construct. In this study, a well-established, self-assembling peptide system was employed to generate a laminin-like bioink to provide signals of cell adhesion and lumen formation in cancer stem cells. One bioink formulation led to the formation of lumen with outperforming characteristics, which showed good stability of the printed construct.

Supramolecular Self-Assembly-Facilitated Aggregation of Tumor-Specific Transmembrane Receptors for Signaling Activation and Converting Immunologically Cold to Hot Tumors.

Supramolecular self-assembling peptide systems are attracting increasing interest in the field of cancer theranostics. Additionally, transformation of the immunologically cold tumor microenvironment into hot is of great importance for obtaining high antitumor responses for most immunotherapies. However, as far as it is known, there are nearly no studies on self-assembling peptides reported to be able to convert cold to hot tumors. Herein, a self-assembling peptide-based cancer theranostic agent (named DBT-2FFGYSA) is designed and synthesized, which can target tumor-specific transmembrane Eph receptor A2 (EphA2) receptors selectively and make the receptors form large aggregates. Such aggregate formation promotes the cross-phosphorylations among EphA2 receptors, leading to signal transduction of antitumor pathway. As a consequence, DBT-2FFGYSA can not only visualize EphA2 receptors in a fluorescence turn-on manner, but also specifically suppress the EphA2 receptor-overexpressed cancer cell proliferation and tumor growth. What is more, DBT-2FFGYSA also serves as an effective agent to convert immunologically cold tumors to hot by inducing the immunogenic cell death of EphA2 receptor-overexpressed cancer cells and recruiting massive tumor-infiltrating T cells. This study, thus, introduces a new category of agents capable of converting cold to hot tumors by pure supramolecular self-assembly without any aid of known anticancer drugs.

Ordered Nanofibers Fabricated from Hierarchical Self-Assembling Processes of Designed α-Helical Peptides.

Peptide self-assembly is fast evolving into a powerful method for the development of bio-inspired nanomaterials with great potential for many applications, but it remains challenging to control the self-assembling processes and nanostrucutres because of the intricate interplay of various non-covalent interactions. A group of 28-residue α-helical peptides is designed including NN, NK, and HH that display distinct hierarchical events. The key of the design lies in the incorporation of two asparagine (Asn) or histidine (His) residues at the a positions of the second and fourth heptads, which allow one sequence to pack into homodimers with sticky ends through specific interhelical Asn-Asn or metal complexation interactions, followed by their longitudinal association into ordered nanofibers. This is in contrast to classical self-assembling helical peptide systems consisting of two complementary peptides. The collaborative roles played by the four main non-covalent interactions, including hydrogen-bonding, hydrophobic interactions, electrostatic interactions, and metal ion coordination, are well demonstrated during the hierarchical self-assembling processes of these peptides. Different nanostructures, for example, long and short nanofibers, thin and thick fibers, uniform metal ion-entrapped nanofibers, and polydisperse globular stacks, can be prepared by harnessing these interactions at different levels of hierarchy.

Supramolecular self-assembling peptides to deliver bone morphogenetic proteins for skeletal regeneration.

Recombinant human bone morphogenetic proteins (BMPs) have shown clinical success in promoting bone healing, but they are also associated with unwanted side effects. The development of improved BMP carriers that can retain BMP at the defect site and maximize its efficacy would decrease the therapeutic BMP dose and thus improve its safety profile. In this review, we discuss the advantages of using self-assembling peptides, a class of synthetic supramolecular biomaterials, to deliver recombinant BMPs. Peptide amphiphiles (PAs) are a broad class of self-assembling peptides, and the use of PAs for BMP delivery and bone regeneration has been explored extensively over the past decade. Like many self-assembling peptide systems, PAs can be designed to form nanofibrous supramolecular biomaterials in which molecules are held together by non-covalent bonds. Chemical and biological functionality can be added to PA nanofibers, through conjugation of chemical moieties or biological epitopes to PA molecules. For example, PA nanofibers have been designed to bind heparan sulfate, a natural polysaccharide that is known to bind BMPs and potentiate their signal. Alternatively, PA nanofibers have been designed to synthetically mimic the structure and function of heparan sulfate, or to directly bind BMP specifically. In small animal models, these bio-inspired PA materials have shown the capacity to promote bone regeneration using BMP at doses 10-100 times lower than established therapeutic doses. These promising results have motivated further evaluation of PAs in large animal models, where their safety and efficacy must be established before clinical translation. We conclude with a discussion on the possiblity of combining PAs with other materials used in orthopaedic surgery to maximize their utility for clinical translation.

Tube to ribbon transition in a self-assembling model peptide system

Peptides that self-assemble into β-sheet rich aggregates are known to form a large variety of supramolecular shapes, such as ribbons, tubes or sheets. However, the underlying thermodynamic driving forces for such different structures are still not fully understood, limiting their potential applications. In the AnK peptide system (A = alanine, K = lysine), a structural transition from tubes to ribbons has been shown to occur upon an increase of the peptide length, n, from 6 to 8. In this work we analyze this transition by means of a simple thermodynamic model. We consider three energy contributions to the total free energy: an interfacial tension, a penalty for deviating from the optimal β-sheet twist angle, and a hydrogen bond deformation when the β-sheets adopt a specific self-assembled structure. Whilst the first two contributions merely provide similar constant energy offsets, the hydrogen bond deformations differ depending on the studied structure. Consequently, the tube structure is thermodynamically favored for shorter AnK peptides, with a crossover at n≈ 13. This qualitative agreement of the model with the experimental observations shows, that we have achieved a good understanding of the underlying thermodynamic features within the self-assembling AnK system.

Independent control of matrix adhesiveness and stiffness within a 3D self-assembling peptide hydrogel

A cell’s insoluble microenvironment has increasingly been shown to exert influence on its function. In particular, matrix stiffness and adhesiveness strongly impact behaviors such as cell spreading and differentiation, but materials that allow for independent control of these parameters within a fibrous, stromal-like microenvironment are very limited. In the current work, we devise a self-assembling peptide (SAP) system that facilitates user-friendly control of matrix stiffness and RGD (Arg-Gly-Asp) concentration within a hydrogel possessing a microarchitecture similar to stromal extracellular matrix. In this system, the RGD-modified SAP sequence KFE-RGD and the scrambled sequence KFE-RDG can be directly swapped for one another to change RGD concentration at a given matrix stiffness and total peptide concentration. Stiffness is controlled by altering total peptide concentration, and the unmodified base peptide KFE-8 can be included to further increase this stiffness range due to its higher modulus. With this tunable system, we demonstrate that human mesenchymal stem cell morphology and differentiation are influenced by both gel stiffness and the presence of functional cell binding sites in 3D culture. Specifically, cells 24 hours after encapsulation were only able to spread out in stiffer matrices containing KFE-RGD. Upon addition of soluble adipogenic factors, soft gels facilitated the greatest adipogenesis as determined by the presence of lipid vacuoles and PPARγ-2 expression, while increasing KFE-RGD concentration at a given stiffness had a negative effect on adipogenesis. This three-component hydrogel system thus allows for systematic investigation of matrix stiffness and RGD concentration on cell behavior within a fibrous, three-dimensional matrix. Statement of SignificancePhysical cues from a cell’s surrounding environment—such as the density of cell binding sites and the stiffness of the surrounding material—are increasingly being recognized as key regulators of cell function. Currently, most synthetic biomaterials used to independently tune these parameters lack the fibrous structure characteristic of stromal extracellular matrix, which can be important to cells naturally residing within stromal tissues. In this manuscript, we describe a 3D hydrogel encapsulation system that provides user-friendly control over matrix stiffness and binding site concentration within the context of a stromal-like microarchitecture. Binding site concentration and gel stiffness both influenced cell spreading and differentiation, highlighting the utility of this system to study the independent effects of these material properties on cell function.

Human osteoarthritic chondrons outnumber patient- and joint-matched chondrocytes in hydrogel culture-Future application in autologous cell-based OA cartilage repair?

Autologous chondrocyte implantation (ACI) is used in 34-60% for osteoarthritic (OA) cartilage defects, although ACI is neither recommended nor designed for OA. Envisioning a hydrogel-based ACI for OA that uses chondrons instead of classically used chondrocytes, we hypothesized that human OA chondrons may outperform OA chondrocytes. We compared patient- and joint surface-matched human OA chondrons with OA chondrocytes cultured for the first time in a hydrogel, using a self-assembling peptide system. We determined yield, viability, cell numbers, mRNA expression, GAPDH mRNA enzyme activity, Collagen II synthesis (CPII) and degradation (C2C), and sulfated glycosaminoglycan. Ex vivo, mRNA expression was comparable. Over time, significant differences in survival led to 3.4-fold higher OA chondron numbers in hydrogels after 2weeks (p=.002). Significantly, more enzymatically active GAPDH protein indicated higher metabolic activity. The number of cultures that expressed mRNA for Collagen Types I and VI, COMP, aggrecan, VEGF, TGF-β1, and FGF-2 (but not Collagen Types II and X) was different, resulting in a 3.5-fold higher number of expression-positive OA chondron cultures (p<.05). Measuring CPII and C2C per hydrogel, OA chondron hydrogels synthesized more than they degraded Collagen Type II, the opposite was true for OA chondrocytes. Per cell, OA chondrons but not OA chondrocytes displayed more synthesis than degradation. Thus, OA chondrons displayed superior biosynthesis and mRNA expression of tissue engineering and phenotype-relevant genes. Moreover, human OA chondrons displayed a significant survival advantage in hydrogel culture, whose presence, drastic extent, and timescale was novel and is clinically significant. Collectively, these data highlight the high potential of human OA chondrons for OA ACI, as they would outnumber and, thus, surpass OA chondrocytes.

Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition

Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to hold the key to building complex structures from simple monomeric units. Small peptides, in particular ultrashort peptides containing up to seven amino acids, for which our laboratory has found many biomedical applications, exhibit immense potential in this regard. For next-generation applications, more intricate control is required over the self-assembly processes. We seek to find out how subtle moiety variation of peptides can affect self-assembly and nanostructure formation. To this end, we have selected a library of 54 tripeptides, derived from systematic moiety variations from seven tripeptides. Our study reveals that subtle structural changes in the tripeptides can exert profound effects on self-assembly, nanostructure formation, hydrogelation, and even phase transition of peptide nanostructures. By comparing the X-ray crystal structures of two tripeptides, acetylated leucine-leucine-glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we obtained valuable insights into the structural factors that can influence the formation of supramolecular peptide structures. We believe that our results have major implications on the understanding of the factors that affect peptide self-assembly. In addition, our findings can potentially assist current computational efforts to predict and design self-assembling peptide systems for diverse biomedical applications.

Structural Basis for Aza-Glycine Stabilization of Collagen.

Previously, we have demonstrated that replacement of the strictly conserved glycine in collagen with aza-glycine provides a general solution for stabilizing triple helical collagen peptides (Chenoweth, D. M.; et al. J. Am. Chem. Soc. 2016, 138, 9751 ; 2015, 137, 12422 ). The additional hydrogen bond and conformational constraints provided by aza-glycine increases the thermal stability and rate of folding in collagen peptides composed of Pro-Hyp-Gly triplet repeats, allowing for truncation to the smallest self-assembling peptide systems observed to date. Here we show that aza-glycine substitution enhances the stability of an arginine-containing collagen peptide and provide a structural basis for this stabilization with an atomic resolution crystal structure. These results demonstrate that a single nitrogen atom substitution for a glycine alpha-carbon increases the peptide's triple helix melting temperature by 8.6 °C. Furthermore, we provide the first structural basis for stabilization of triple helical collagen peptides containing aza-glycine and we demonstrate that minimal alteration to the peptide backbone conformation occurs with aza-glycine incorporation.

Controlled Sub-Nanometer Epitope Spacing in a Three-Dimensional Self-Assembled Peptide Hydrogel.

Cells in the body use a variety of mechanisms to ensure the specificity and efficacy of signal transduction. One way that this is achieved is through tight spatial control over the position of different proteins, signaling sequences, and biomolecules within and around cells. For instance, the extracellular matrix protein fibronectin presents RGDS and PHSRN sequences that synergistically bind the α5β1 integrin when separated by 3.2 nm but are unable to bind when this distance is >5.5 nm.1 Building biomaterials to controllably space different epitopes with subnanometer accuracy in a three-dimensional (3D) hydrogel is challenging. Here, we synthesized peptides that self-assemble into nanofiber hydrogels utilizing the β-sheet motif, which has a known regular spacing along the peptide backbone. By modifying specific locations along the peptide, we are able to controllably space different epitopes with subnanometer accuracy at distances from 0.7 nm to over 6 nm, which is within the size range of many protein clusters. Endothelial cells encapsulated within hydrogels displaying RGDS and PHSRN in the native 3.2 nm spacing showed a significant upregulation in the expression of the alpha 5 integrin subunit compared to those in hydrogels with a 6.2 nm spacing, demonstrating the physiological relevance of the spacing. Furthermore, after 24 h the cells in hydrogels with the 3.2 nm spacing appeared to be more spread with increased staining for the α5β1 integrin. This self-assembling peptide system can controllably space multiple epitopes with subnanometer accuracy, demonstrating an exciting platform to study the effects of ligand density and location on cells within a synthetic 3D environment.

RANKL release from self-assembling nanofiber hydrogels for inducing osteoclastogenesis in vitro.

To develop a nanofiber hydrogel (NF-hydrogel) for sustained and controlled release of the recombinant receptor activator of NF-kB ligand; (RANKL) and to characterize the release kinetics and bioactivity of the released RANKL. Various concentrations of fluorescently-labelled RANKL protein were added to NF-hydrogels, composed of Acetyl-(Arg-Ala-Asp-Ala)4-CONH2 [(RADA)4] of different concentrations, to investigate the resulting in vitro release rates. The nano-structures of NF-hydrogel, with and without RANKL, were determined using atomic force microscopy (AFM). Released RANKL was further analyzed for changes in secondary and tertiary structure using CD spectroscopy and fluorescent emission spectroscopy, respectively. Bioactivity of released RANKL protein was determined using NFATc1 gene expression and tartrate resistant acid phosphatase (TRAP) activity of osteoclast cells as biomarkers. NF-hydrogel concentration dependent sustained release of RANKL protein was measured at concentrations between 0.5 and 2%(w/v). NF-hydrogel at 2%(w/v) concentration exhibited a sustained and slow-release of RANKL protein up to 48h. Secondary and tertiary structure analyses confirmed no changes to the RANKL protein released from NF-hydrogel in comparison to native RANKL. The results of NFATc1 gene mRNA expression and TRAP activities of osteoclast, showed that the release process did not affect the bioactivity of released RANKL. This novel study is the first of its kind to attempt in vitro characterization of NF-hydrogel based delivery of RANKL protein to induce osteoclastogenesis. We have shown the self-assembling NF-hydrogel peptide system is amenable to the sustained and controlled release of RANKL locally; that could in turn increase local concentration of RANKL to induce osteoclastogenesis, for application to the controlled mobilization of tooth movement in orthodontic procedures. Orthodontic tooth movement (OTM) occurs through controlled application of light forces to teeth, facilitating the required changes in the surrounding alveolar bone through the process of bone remodelling. The RANKL system regulates alveolar bone remodelling and controls root resorption during OTM. The use of exogenous RANKL to accelerate OTM has not been attempted to date because large quantities of RANKL for systemic therapy may subsequently cause serious systemic loss of skeletal bone. The controlled and sustained local release of RANKL from a carrier matrix could maximize its therapeutic benefit whilst minimizing systemic side effects. In this study a NF-hydrogel was used for sustained and controlled release of RANKL and the release kinetics and biofunctionality of the released RANKL was characterized. Our results provide fundamental insight for further investigating the role of RANKL NF-hydrogel release systems for inducing osteoclastogenesis in vivo.

General Solution for Stabilizing Triple Helical Collagen.

One of the most ubiquitous stabilizing forces in nature is the hydrogen bond, exemplified by the folded secondary, tertiary, and higher-order structure of biomolecules. Despite the fundamental importance of hydrogen bonding, dependence on this stabilizing force places limitations on nature's proteinogenic building blocks. Herein, we demonstrate that replacement of the strictly conserved glycine in collagen with aza-glycine has profound consequences on the stability and self-assembly of collagen peptides by providing an extra hydrogen bond donor. The additional hydrogen bond provided by aza-glycine allows for complete replacement of glycine residues in collagen peptides and truncation to the smallest self-assembling collagen peptide systems observed to date. Our results highlight the vital importance of hydrogen bonding at desolvated interfaces, providing a new strategy for optimization of designed peptide materials and a general solution for stabilizing the collagen triple helix.

Characterisation of minimalist co-assembled fluorenylmethyloxycarbonyl self-assembling peptide systems for presentation of multiple bioactive peptides

The nanofibrillar structures that underpin self-assembling peptide (SAP) hydrogels offer great potential for the development of finely tuned cellular microenvironments suitable for tissue engineering. However, biofunctionalisation without disruption of the assembly remains a key issue. SAPS present the peptide sequence within their structure, and studies to date have typically focused on including a single biological motif, resulting in chemically and biologically homogenous scaffolds. This limits the utility of these systems, as they cannot effectively mimic the complexity of the multicomponent extracellular matrix (ECM). In this work, we demonstrate the first successful co-assembly of two biologically active SAPs to form a coassembled scaffold of distinct two-component nanofibrils, and demonstrate that this approach is more bioactive than either of the individual systems alone. Here, we use two bioinspired SAPs from two key ECM proteins: Fmoc-FRGDF containing the RGD sequence from fibronectin and Fmoc-DIKVAV containing the IKVAV sequence from laminin. Our results demonstrate that these SAPs are able to co-assemble to form stable hybrid nanofibres containing dual epitopes. Comparison of the co-assembled SAP system to the individual SAP hydrogels and to a mixed system (composed of the two hydrogels mixed together post-assembly) demonstrates its superior stable, transparent, shear-thinning hydrogels at biological pH, ideal characteristics for tissue engineering applications. Importantly, we show that only the coassembled hydrogel is able to induce in vitro multinucleate myotube formation with C2C12 cells. This work illustrates the importance of tissue engineering scaffold functionalisation and the need to develop increasingly advanced multicomponent systems for effective ECM mimicry. Statement of SignificanceSuccessful control of stem cell fate in tissue engineering applications requires the use of sophisticated scaffolds that deliver biological signals to guide growth and differentiation. The complexity of such processes necessitates the presentation of multiple signals in order to effectively mimic the native extracellular matrix (ECM). Here, we establish the use of two biofunctional, minimalist self-assembling peptides (SAPs) to construct the first co-assembled SAP scaffold. Our work characterises this construct, demonstrating that the physical, chemical, and biological properties of the peptides are maintained during the co-assembly process. Importantly, the coassembled system demonstrates superior biological performance relative to the individual SAPs, highlighting the importance of complex ECM mimicry. This work has important implications for future tissue engineering studies.

Multiplexing natural orientation: oppositely directed self-assembling peptides.

We explore here the possibility that polypeptide chains with directional multiplicity might provide for the control of peptide self-assembly processes. We tested this new possibility using an oppositely directed peptide (ODP) supramolecular system. The ODP could make it possible to form a βαβ motif with antiparallel β-sheets, which does not exist in nature. Furthermore, the designed ODPs were able to self-assemble into discrete, homogeneous, and structured protein-like controlled nano-objects. ODPs represent a simple but powerful unnatural self-assembling peptide system that can become a basic scaffold for fabricating more complex and elaborate artificial nanostructures.

Nanomaterials based on peptides

Owing to the assortment of functional groups, peptides are capable of self-assembly and formation of regularly patterned supramolecular complexes. Peptide-based nanomaterials offer promise for medicine, engineering, and bioimaging. The present review surveys the structure and characteristics of filaments formed by peptides of various secondary structures and their further assembly into 2D and 3D nanomaterials. Possible application areas of self-assembling peptide systems, including the synthesis of inorganic nanomaterials, are considered.

Designer nanomaterials using chiral self-assembling peptide systems and their emerging benefit for society

Chirality is absolutely central in chemistry and biology. The recent findings of chiral self-assembling peptides' remarkable chemical complementarity and structural compatibility make it one of the most inspired designer materials and structures in nanobiotechnology. The emerging field of designer chemistry and biology further explores biological and medical applications of these simple D,L- amino acids through producing marvellous nanostructures under physiological conditions. These self-assembled structures include well-ordered nanofibers, nanotubes and nanovesicles. These structures have been used for 3-dimensional tissue cultures of primary cells and stem cells, sustained release of small molecules, growth factors and monoclonal antibodies, accelerated wound-healing in reparative and regenerative medicine as well as tissue engineering. Recent advances in molecular designs have also led to the development of 3D fine-tuned bioactive tissue culture scaffolds. They are also used to stabilize membrane proteins including difficult G-protein coupled receptors for designing nanobiodevices. One of the self-assembling peptides has been used in human clinical trials for accelerated wound-healings. It is our hope that these peptide materials will open doors for more and diverse clinical uses. The field of chiral self-assembling peptide nanobiotechnology is growing in a number of directions that has led to many surprises in areas of novel materials, synthetic biology, clinical medicine and beyond.

Design of Self-Assembling Peptides and Their Biomedical Applications

Combining physics, engineering, chemistry and biology, we can now design, synthesize and fabricate biological nanomaterials at the molecular scale using self-assembling peptide systems. These peptides have been used for fabrication of nanomaterials, including nanofibers, nanotubes and vesicles, nanometer-thick surface coating and nanowires. Some of these peptides are used for stabilizing membrane proteins and drug delivery, and others provide a more permissive environment for 3D cell culture, tissue engineering and repair of tissues in regenerative medicine. Self-assembling peptides are also useful for fabricating a wide spectrum of exquisitely fine architectures, nanomaterials and nanodevices for nanomedicine and nanobiotechnology. These peptide systems lie at the interface between molecular biology, chemistry, materials science and engineering. The studies of designed self-assembling peptides and their applications will help us to understand nature?s enormous power and how to apply it to benefit other disciplines and society.