Harsimran Kaur

Bio: Harsimran Kaur is an academic researcher. The author has contributed to research in topics: Self-healing hydrogels & Peptide amphiphile. The author has an hindex of 4, co-authored 6 publications receiving 46 citations.

Accessing Highly Tunable Nanostructured Hydrogels in a Short Ionic Complementary Peptide Sequence via pH Trigger.

Abstract: Creating diverse nanostructures from a single gelator through modulating the self-assembly pathway has been gaining much attention in recent years. To this direction, we are exploring the effect of modulation of pH as a potential self-assembly pathway in governing the physicochemical properties of the final gel phase material. In this context, we used a classical nongelator with the ionic complementary sequence FEFK, which was rationally conjugated to an aromatic group naphthoxyacetic acid (Nap) at the N-terminal end to tune its gelation behavior. Interestingly, the presence of oppositely charged amino acids in the peptide amphiphile resulted in pH-responsive behavior, leading to the formation of hydrogels over a wide pH range (2.0-12.0); however, their structures differ significantly at the nanoscale. Thus, by simply manipulating the overall charge over the exposed surface of the peptide amphiphiles as a function of pH, we were able to access diverse self-assembled nanostructures within a single gelator domain. The charged state of the gelator at the extreme pH (2.0, 12.0) led to a thinner fiber formation, in contrast to the thicker fibers observed near the physiological pH owing to charge neutralization, thus promoting the lateral association. Such variation in molecular packing was found to be further reflected in the variable mechanical strengths of the peptide hydrogels obtained at different pH values. Moreover, the gelation of the peptide at physiological pH offers an additional advantage to explore this hydrogel as a cell culture scaffold. We anticipate that our study on controlling the self-assembly pathway of the ionic complementary peptide amphiphile can be an elegant approach to access diverse self-assembled materials, which can expand the zone of its applicability as a stimuli-responsive biomaterial.

Designing a Tenascin-C-Inspired Short Bioactive Peptide Scaffold to Direct and Control Cellular Behavior.

Abstract: Over the last decade, synthetically designed scaffolds are emerging as promising biomaterials for tissue engineering applications. In this context, peptide hydrogels are gaining wide attention, owing to their ability to mimic structural and functional complexity of the natural extracellular matrix (ECM). To this end, exploration of minimalistic bioactive peptide sequences for the fabrication of tissue engineering scaffolds provides a competitive edge over the conventional design principles where complex sequences were mainly explored for scaffold formation. In the present study, we explored the self-assembling potential of minimalistic bioactive peptide sequence from tenascin-C protein and its application in supporting cellular viability and proliferation. Tenascin-C is a multimeric protein known to express in adult tissues mainly during tissue injury or remodeling. To the best of our knowledge, the designed octapeptide is the shortest bioactive sequence derived solely from tenascin-C, which is known in the literature to impart specific bioactivity. The short peptide sequence showed high propensity to form a nanofibrous network at physiological pH, which was further entangled to form a macroscopic hydrogel network. Interestingly, the gels were found to be mechanoresponsive and thixotropic which opens up the scope for utilizing them as designer injectable matrices. These novel hydrogels supported the growth and proliferation of cells of both neural and non-neural ECM origin. However, neural cells cultured on these bioactive hydrogels showed normal β-III tubulin expression, highlighting their specific potential to be further explored for tissue engineering applications.

Pathway-Dependent Preferential Selection and Amplification of Variable Self-Assembled Peptide Nanostructures and Their Biological Activities.

Abstract: We demonstrate the formation of diverse peptide nanostructures, which are "out of equilibrium" based on a single dipeptide gelator. These structures represent the differential energy states of the free energy landscape, which are accessed by differential energy inputs provided by variable self-assembly pathways, that is, heat-cool method or ultrasonication. A higher energy input by the heat-cool method created a thermodynamically favored long entangled nanofibrillar network, while twisted ribbonlike structures were prevalent by ultrasonication. Interestingly, the nanofibrillar network representing the global thermodynamic minima could be accessed by simply melting the kinetically trapped structures as indicated by the thermoreversibility studies. The impact on the material strength was remarkable; gels with an order of magnitude difference in mechanical properties could be fabricated by simply modulating the self-assembly pathways. Interestingly, the thermodynamically favored nanofibrous network promoted cellular adhesion and survival, while a significant number of cells fail to adhere on the kinetically trapped twisted ribbons. Thus, nonequilibrium nanostructures open up new directions to develop advanced functional materials with diverse functions.

Designing aromatic N-cadherin mimetic short-peptide-based bioactive scaffolds for controlling cellular behaviour

Abstract: The development of suitable biomaterials is one of the key factors responsible for the success of the tissue-engineering field. Recently, significant effort has been devoted to the design of biomimetic materials that can elicit specific cellular responses and direct new tissue formation mediated by bioactive peptides. The success of the design principle of such biomimetic scaffolds is mainly related to the cell–extracellular matrix (ECM) interactions, whereas cell–cell interactions also play a vital role in cell survival, neurite outgrowth, attachment, migration, differentiation, and proliferation. Hence, an ideal strategy to improve cell–cell interactions would rely on the judicious incorporation of a bioactive motif in the designer scaffold. In this way, we explored for the first time the primary functional pentapeptide sequence of the N-cadherin protein, HAVDI, which is known to be involved in cell–cell interactions. We have formulated the shortest N-cadherin mimetic peptide sequence utilizing a minimalistic approach. Furthermore, we employed a classical molecular self-assembly strategy through rational modification of the basic pentapeptide motif of N-cadherin, i.e. HAVDI, using Fmoc and Nap aromatic moieties to modify the N-terminal end. The designed N-cadherin mimetic peptides, Fmoc-HAVDI and Nap-HAVDI, self-assembled to form a nanofibrous network resulting in a bioactive peptide hydrogel at physiological pH. The nanofibrous network of the pentapeptide hydrogels resembles the topology of the natural ECM. Furthermore, the mechanical strength of the gels also matches that of the native ECM of neural cells. Interestingly, both the N-cadherin mimetic peptide hydrogels supported cell adhesion and proliferation of the neural and non-neural cell lines, highlighting the diversity of these peptidic scaffolds. Further, the cultured neural and non-neural cells on the bioactive scaffolds showed normal expression of β-III tubulin and actin, respectively. The cellular response was compromised in control peptides, which further establishes the significance of the bioactive motifs towards controlling the cellular behaviour. Our study indicated that our designer N-cadherin-based peptidic hydrogels mimic the structural as well as the physical properties of the native ECM, which has been further reflected in the functional attributes offered by these scaffolds, and thus offer a suitable bioactive domain for further use as a next-generation material in tissue-engineering applications.

A review on recent advances in polymer and peptide hydrogels

Abstract: In this review, we focus on the very recent developments on the use of the stimuli responsive properties of polymer hydrogels for targeted drug delivery, tissue engineering, and biosensing utilizing their different optoelectronic properties. Besides, the stimuli-responsive hydrogels, the conducting polymer hydrogels are discussed, with specific attention to the energy generation and storage behavior of the xerogel derived from the hydrogel. The electronic and ionic conducting gels have been discussed that have applications in various electronic devices, e.g., organic field effect transistors, soft robotics, ionic skins, and sensors. The properties of polymer hybrid gels containing carbon nanomaterials have been exemplified here giving attention to applications in supercapacitors, dye sensitized solar cells, photocurrent switching, etc. Recent trends in the properties and applications of some natural polymer gels to produce thermal and acoustic insulating materials, drug delivery vehicles, self-healing material, tissue engineering, etc., are discussed. Besides the polymer gels, peptide gels of different dipeptides, tripeptides, oligopeptides, polypeptides, cyclic peptides, etc., are discussed, giving attention mainly to biosensing, bioimaging, and drug delivery applications. The properties of peptide-based hybrid hydrogels with polymers, nanoparticles, nucleotides, fullerene, etc., are discussed, giving specific attention to drug delivery, cell culture, bio-sensing, and bioimaging properties. Thus, the present review delineates, in short, the preparation, properties, and applications of different polymer and peptide hydrogels prepared in the past few years.

Peptide-Based Supramolecular Systems Chemistry.

Abstract: Peptide-based supramolecular systems chemistry seeks to mimic the ability of life forms to use conserved sets of building blocks and chemical reactions to achieve a bewildering array of functions. Building on the design principles for short peptide-based nanomaterials with properties, such as self-assembly, recognition, catalysis, and actuation, are increasingly available. Peptide-based supramolecular systems chemistry is starting to address the far greater challenge of systems-level design to access complex functions that emerge when multiple reactions and interactions are coordinated and integrated. We discuss key features relevant to systems-level design, including regulating supramolecular order and disorder, development of active and adaptive systems by considering kinetic and thermodynamic design aspects and combinatorial dynamic covalent and noncovalent interactions. Finally, we discuss how structural and dynamic design concepts, including preorganization and induced fit, are critical to the ability to develop adaptive materials with adaptive and tunable photonic, electronic, and catalytic properties. Finally, we highlight examples where multiple features are combined, resulting in chemical systems and materials that display adaptive properties that cannot be achieved without this level of integration.

Ultrashort Peptide Self-Assembly: Front-Runners to Transport Drug and Gene Cargos.

Abstract: The translational therapies to promote interaction between cell and signal come with stringent eligibility criteria. The chemically defined, hierarchically organized, and simpler yet blessed with robust intermolecular association, the peptides, are privileged to make the cut-off for sensing the cell-signal for biologics delivery and tissue engineering. The signature service and insoluble network formation of the peptide self-assemblies as hydrogels have drawn a spell of research activity among the scientists all around the globe in the past decades. The therapeutic peptide market players are anticipating promising growth opportunities due to the ample technological advancements in this field. The presence of the other organic moieties, enzyme substrates and well-established protecting groups like Fmoc and Boc etc., bring the best of both worlds. Since the large sequences of peptides severely limit the purification and their isolation, this article reviews the account of last 5 years' efforts on novel approaches for formulation and development of single molecule amino acids, ultra-short peptide self-assemblies (di- and tri- peptides only) and their derivatives as drug/gene carriers and tissue-engineering systems.