Introduction to peptide soft materials

Arindam Banerjee

Arindam Banerjee is a full professor in the School of Biological Sciences, Indian Association for the Cultivation of Science, Kolkata, India. He received his MSc from Bisva-Bharati University, Santiniketan, India and his PhD from Indian Institute of Science, Bangalore, India. He was a postdoctoral fellow at Weizmann Institute of Science, Israel for a short period of time. His research group investigates self-assembly of peptides and amino acid derivatives; smart soft materials, stimuli-responsive gels, and multipurpose uses of these gels in drug delivery, antibacterial applications, and environmental remediation; organic–inorganic functional nanohybrids; fluorescent noble metal nanoclusters and carbon dots. He is a fellow of the Royal Society of Chemistry (RSC), UK (FRSC) and a fellow of the Indian Academy of Sciences (Bangalore), India. He is an Advisory Board member of Soft Matter.

Ian W. Hamley

Professor Ian W. Hamley is Diamond Professor of Physical Chemistry at the University of Reading. He has more than 25 years’ experience of research on different types of soft materials, including peptides, polymers, liquid crystals and surfactants. He received a Royal Society Wolfson Research Merit Award in 2011, the RSC Peter Day Award for Materials Chemistry (2016) and the MacroGroup UK Medal (2017). His research programme focuses on the self-assembly of peptide materials and its relationship to bioactivity. He has supervised more than fifty postdoctoral and postgraduate researchers and has published over 400 papers and five authored books as well as many edited books and chapters.

Peptides are versatile biomolecules which can be used to design innovative functional and structural soft materials. This themed issue is devoted to a selection of highlights of research from leading teams around the world, working in this rapidly developing field. Peptides can now be created to produce soft materials with a huge range of properties and applications using recently established molecular design rules based on sequence, residue properties and defined secondary structure. Peptides can be synthesized at high yield and purity with advanced and automated methods, and new methods are being developed to create new kinds of peptide-based and peptide-inspired constructs and conjugates. The design of peptide sequences is no longer limited to the use of the 20 natural amino acids, because non-proteinogenic and unusual amino acid residues can be incorporated within peptides using a variety of recently-developed chemical and chemical biology approaches. Peptide self-assembly can be driven by a range of non-covalent interactions including hydrogen bonding, electrostatic interactions, π–π and hydrophobic interactions. This, often coupled with peptide secondary structure formation, leads to a range of soft materials under suitable conditions. Self-assembling peptides can form different soft nano-structures including nanospheres (micelles), vesicles, nanotubes, nanofibrils, nanosheets, ribbons, and nanofilms.^1–7 Peptide-based hydrogels are important peptide-based soft materials that exhibit fascinating properties such as excellent biocompatibility, tunable mechanical stiffness, thermal stability and stimulus-responsiveness. The mechanical strength of such gels can be easily regulated by varying the peptide structure, solvent, pH, ionic strength of the medium, the presence of additives, etc. Similarly, the thermal stability of these gels can be varied by altering any of the above mentioned parameters. Regulation of the thermal and mechanical properties of these gels can tune their functions. Moreover, the responsiveness of peptide hydrogels to chemical, physical and biological stimuli^8,9 makes them very useful for many biological and other applications. Apart from having tuneable structural properties, peptide gels have various applications in health care,¹⁰ environmental remediation¹¹ and as renewable non-conventional energy sources.¹² These gels form a three-dimensional network structure from self-assembling peptide-based nanofibers that entrap solvents, often at low peptide content. Peptide hydrogels provide porous structures that aid cell migration and growth. They also have the ability to offer an environment that mimics the extra-cellular matrix, and this opens up opportunities for different biomedical applications including drug delivery, 3D cell culture, tissue engineering, wound healing, antimicrobial agents and 3D bio-printing.^13,14 Due to their high water content and extra-cellular matrix like properties, these hydrogels offer an excellent platform even for three-dimensional neural tissue culture.¹⁵ Peptide-based hydrogels can be used to regulate the differentiation of stem cells, and in cancer therapy.¹⁶

Self-assembling peptide/amino acid-based soft-materials have also found applications in nanotechnology, to fabricate metal nanoparticles, ultra-small fluorescent silver nanoclusters,^17,18 as well as new hybrid nanomaterials.¹⁹ Peptide- and amino acid-based hydrogels have also been used to recover toxic organic dyes and toxic metal ions from wastewater.²⁰ Organogels of these biomolecules have been demonstrated to have remarkable properties, such as the ability to gel oils from oil–water mixtures in a phase selective gelation process, useful for oil spill recovery.²¹ Structural modifiability coupled with functional diversity make such gels very valuable for health care applications and waste-water management.

This themed issue encompasses a multidisciplinary field in soft matter science, based on self-assembling peptides or amino acids and their derivatives. The papers discuss the self-assembly of a huge diversity of peptide-based molecules, analyzed using a number of cutting-edge methods with an incredible range of end-uses. Several papers discuss peptide-based gels that result from the interplay of various physical interactions that leads to gel formation, as well as a number of important applications of these gels. In this themed issue (which includes all the papers referenced by DOI below), we bring together a diverse range of papers on peptide soft materials, which highlight recent advances and lay the foundations for future development of new kinds of next generation peptide soft materials.

Xu and co-workers show that the hydrogelation of a branched peptide leads to a stronger gel after the enzymatic cleavage of the branch from the precursor peptide. This study shows enzyme assisted production of dynamic soft materials (DOI: 10.1039/d0sm00867b). Another report in this issue discusses the interaction of a fluorescently-labelled protein (human serum albumin) modified with a polymer-binding peptide, and it is shown that the fluorescence property is thermo-responsive providing an affinity-based thermo-responsive fluorescence switch (DOI: 10.1039/d0sm01107j). Nilsson and co-workers investigate how the formulation of phenylalanine-based hydrogels impacts their mechano-responsiveness or thixotropic properties, which is very important for biomedical applications (DOI: 10.1039/d0sm01217c). Another interesting study includes a comparative investigation of stereoisomers and structural isomers of a series of unprotected dipeptides in terms of aggregate formation and hydrogelation (DOI: 10.1039/d0sm01191f). Lin and co-workers vividly demonstrate the impact of fluoro-substitution and electrostatic interactions on self-assembly and hydrogelation of N-terminally protected tripeptides and the regulation of gel stiffness of co-assembled hydrogels (DOI: 10.1039/d0sm01186j). In another contribution, time-dependent phenomena underpinning the formation of macroscopic membranes from the co-assembly of cationic beta-peptides and anionic alginate solution are carefully examined, and the membrane structure development is shown to depend on the aging process (DOI: 10.1039/d0sm01197e). Another interesting report describes the oligomerisation and aggregation of semaglutide, an important therapeutic peptide. This was thoroughly examined using a combination of UV-visible, fluorescence spectroscopic and electronic circular dichroism studies as well as molecular dynamics simulations. These methods indicate the presence of monomeric and dimeric species, a monomer-to-dimer transition and the formation of higher oligomers and other aggregates after extended times (DOI: 10.1039/d0sm01011a). Haldar and co-workers demonstrate acid-induced assembly and urease-assisted disassembly of fibrils formed by the self-assembly of N-terminally protected phenylalanine and transient hydrogelation (DOI: 10.1039/d0sm00774a). Adler-Abramovich, Accardo and co-workers have successfully demonstrated the self-assembly and hydrogelation of a series of PEGylated hexapeptides incorporating non-coded amino acids including naphthylalanine (Nal) and dopamine (Dopa), and they investigated the effect of chemical modification and substitution of residues on the structural and mechanical properties of these gels (DOI: 10.1039/d0sm00825g). Another noteworthy contribution demonstrates the aging effect on the thermal, mechanical and fluorescence properties of hydrogels formed by a histidine-containing peptide conjugated to the rigid aromatic unit naphthalenediimide. This reveals a remarkable example of the increase in thermal and mechanical stabilities of co-assembled hydrogels with time (DOI: 10.1039/d0sm00468e). Brimble and co-workers demonstrate the directed self-association of an octapeptide thiophene–diketopyrrolopyrrole conjugate in water media at different pHs and they have used this as a platform to create a bio-organic film (DOI: 10.1039/d0sm01071e). Silva and co-workers report on the self-assembly of a cationic heptapeptide derived from a Trojan cell-penetrating peptide, penetratin, and the intracellular delivery of DNA using this self-assembled peptide (DOI: 10.1039/d0sm00347f). A further paper describes the self-assembly of a model lipopeptide in cyclohexane–water systems which leads to the formation of micelles, and the formation of various polymorphs with cluster aggregates is also noted. Moreover, these soft materials exhibit notable catalytic properties for an asymmetric aldol reaction (DOI: 10.1039/d0sm00245c). Another remarkable finding concerns the self-assembly of a peptide derivative containing a hydrazone bond and the transient hydrogel formation activated by a hydrazone–oxime exchange reaction (DOI: 10.1039/c9sm01969c). This collection also includes several valuable reviews pertaining to various biomedical applications of peptide based hydrogels in potential therapeutics, diagnostics, and drug delivery agents (DOI: 10.1039/d0sm01136c; DOI: 10.1039/d0sm01198c; DOI: 10.1039/d0sm00885k; DOI: 10.1039/d0sm00966k).

The structural diversity, functional adaptability, biocompatibility, easy formulation, stimuli-responsiveness and widespread potential applications of peptide-based assemblies make this an exciting emerging area in soft matter science, as exemplified by the excellent contributions to this themed issue. This research should lead to a plethora of next generation smart materials in the near future.

Acknowledgements

Ian W. Hamley acknowledges project funding provided by the EPSRC (grant number EP/L020599/1).

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