Chiral biointerface materials

Chiral phenomena are ubiquitous in nature from macroscopic to microscopic, including the high chirality preference of small biomolecules, special steric conformations of biomacromolecules induced by it, as well as chirality-triggered biological and physiological processes. The introduction of chirality into the study of interface interactions between materials and biological systems leads to the generation of chiral biointerface materials, which provides a new platform for understanding the chiral phenomena in biological system, as well as the development of novel biomaterials and devices. This critical review gives a brief introduction to the recent advances in this field. We start from the fabrication of chiral biointerface materials, and further investigate the stereo-selective interaction between biological systems and chiral interface materials to find out key factors governing the performance of such materials in given conditions, then introduce some special functionalities and potential applications of chiral biointerface materials, and finally present our own thinking about the future development of this area (108 references).     

Chiral polymer-based biointerface materials

Chirality is a unique phenomenon in nature. Chiral interactions play an important role in biological and physiological processes, which provides much inspiration for scientists to develop chiral materials. As a breakthrough from traditional materials, biointerface materials based on chiral polymers have attracted increasing interest over the past few years. Such materials elegantly combine the advantages of chiral surfaces and traditional polymers, and provide a novel solution not only for the investigation of chiral interaction mechanisms but also for the design of biomaterials with diverse applications, such as in tissue engineering and biocompatible materials, bioregulation, chiral separation and chiral sensors. Herein, we summarize recent advances in the study of chiral effects and applications of chiral polymer-based biointerface materials, and also present some challenges and perspectives.     

Phenethylamine@Pillar[5]arene Biointerface for Highly Enantioselective Adsorption of Protein

In the life system, the biointerface plays an important role in cell adsorption, platelet adsorption and activation. Therefore, the study of protein adsorption on the biointerface is of great significance for understanding life phenomena and treatment in vitro. In this paper, a chiral biointerface was constructed by the virtue of host‐guest interaction between a water‐soluble pillar[5]arene (WP5) and phenethylamine (PEA) over a gold surface for adsorption of lysozyme proteins. From the experimental results it was identified that the host‐guest biointerface has a high adsorption capacity and strong chiral selectivity. Furthermotre, it was identified that the host‐guest interaction plays the decisive role in the enhancement of chirality of the interface, which was much beneficial for increasing protein adsorption and amplifying the capacity of chiral discrimination. Therefore, this work provides a new idea for the construction of biointerface materials with high protein adsorption capacity and high chiral selectivity through supramolecular interaction, which will have potential applications in the fields of biosensors, biocatalysts, biomaterials.     

Critical aspects of biointerface design and their impact on biosensor development

The stable integration of a biological recognition element on a transducing substrate surface is the single most important step in the creation of a high-functioning sensor surface. The key factors affecting biotic and abiotic functionalities at the biointerface are both chemical and physical. Understanding the interactions between biomolecules and surfaces, and their emergent complexity, is critical for biointerface implementation for sensing applications. In this overview, we highlight materials and methods typically used for biosensor development. Particular emphasis has been given to the experimental evaluation of biointerfacial properties and functionality. Promising research directions for application of biointerfaces to biosensing are suggested.     

Peptide–Protein Interactions: From Drug Design to Supramolecular Biomaterials

The self-recognition and self-assembly of biomolecules are spontaneous processes that occur in Nature and allow the formation of ordered structures, at the nanoscale or even at the macroscale, under thermodynamic and kinetic equilibrium as a consequence of specific and local interactions. In particular, peptides and peptidomimetics play an elected role, as they may allow a rational approach to elucidate biological mechanisms to develop new drugs, biomaterials, catalysts, or semiconductors. The forces that rule self-recognition and self-assembly processes are weak interactions, such as hydrogen bonding, electrostatic attractions, and van der Waals forces, and they underlie the formation of the secondary structure (e.g., α-helix, β-sheet, polyproline II helix), which plays a key role in all biological processes. Here, we present recent and significant examples whereby design was successfully applied to attain the desired structural motifs toward function. These studies are important to understand the main interactions ruling the biological processes and the onset of many pathologies. The types of secondary structure adopted by peptides during self-assembly have a fundamental importance not only on the type of nano- or macro-structure formed but also on the properties of biomaterials, such as the types of interaction, encapsulation, non-covalent interaction, or covalent interaction, which are ultimately useful for applications in drug delivery.     

Modulating cell behaviors on chiral polymer brush films with different hydrophobic side groups

Chirality is one of the significant biochemical signatures of life. Nearly all biological polymers are homochiral as they usually show high preference toward one specific enantiomer. This phenomenon inspires us to design biomaterials with chiral units and study their interactions with cells and other biological entities. In this article, through adopting three pairs of aliphatic amino acids with different hydrophobic side groups as chiral species, and using two adhesive cell lines as examples, we show that the chirality of polymer brushes can trigger differential cell behaviors on the enantiomorphous surfaces, and more interestingly, such chiral effect on cellular behaviors can be modulated in a certain extent by varying the hydrophobic side groups of the chiral moieties composing the polymers. This work not only proves the versatility of the chiral effect at the cell level but also demonstrates a method to bridge the gap between organic signal molecules and biomaterials. It thus points out a promising approach for designing novel biomaterials based on the chiral effect, which will be an important complement for conventional strategies in the study of biomaterials.     

Taking chiral polymers toward immune regulation

The implanted materials and devices can be recognized by the immune system, which in turn mediate the immune microenvironment of tissues. The immune system in mammals is composed of diverse components such as immune cells, cytokines, radicals and antibodies etc. Chiral polymers with good biocompatibility, tailorable ability and ease of fabrication are excellent candidates for diverse biomedical applications. Different chiral biomaterials have been investigated to study the interactions of immune cells and the resulted immune responses, but the effects of chiral polymers on immune regulation are less tackled. Tailoring the chemical and physical properties of chiral polymers can lead to beneficial immune responses. This review focuses on the different fabrication strategies of chiral polymers and interactions of chiral polymers with immune cells and other biological components. The adhesion and interaction patterns of chiral polymers with immune cells, changes in shapes and characteristics of cells, release or inhibition of cytokines, and resulting response are discussed in the review.     

Chiral Nanoprobes and Their Biological Effects

Chirality is an essential property of nature. The emergence of chiral material in nanoscale has shown great promise in the investigation of biological interfaces, chiral optical devices, metamaterials and the origin of chirality. In the present study, we focused on fabricating chiral nanoprobes and their applications in living systems. Through precise synthesis or the self‐assembly of various chiral configurations, significant research achievements have been obtained by our group. In this brief introduction, we will discuss the recent progress of chiral nanostructures in the selective recognition of biomolecules, ultrasensitive detection and their interaction with living cells.     

生物液晶

液晶是一种介于液相和固相之间的中间相，具有流动性和有序性，其性质表明它是一种极适于生命特征的状态。生命体中的蛋白质、核酸、多糖、脂类等都能够通过自组装而呈现液晶态，其液晶行为与细胞和组织功能的表达有关。本文介绍了液晶的分类、表征方法及生命体内的蛋白质、脱氧核糖核酸、多糖、脂类的液晶特性以及液晶态的生物材料与细胞的相互作用。     

Surface perspectives in the biomedical applications of poly(α-hydroxy acid)s and their associated copolymers

Impressive advances in biotechnology, bioengineering, and biomaterials with unique properties have led to increased interest in polymers and other novel materials in biological and biomedical research and development over the past two decades. Although biomaterials have already made an enormous impact in biomedical research and clinical practice, there is a need for better understanding of the surface and interfacial chemistry between tissue (or cells) and biomedical materials. This is because the detailed physicochemical events related to the biological response to the surface of materials still often remain obscure, even though surface properties are important determinants of biomedical material function. In this regard, data available in the literature show the complexity of the interactions (surface reorganization, non-specific/specific protein adsorption, and chemical reactions such as acid-base, ion pairing, ion exchange, hydrogen bonding, divalent-ion bridging) and the interrelationship between biological environments, interfacial properties, and surface functional groups responsible for the biological responses. Because of the multidisciplinary nature of surface and interfacial phenomena at the surface of biomedical polymers, this review focuses on several aspects of current work published on poly(alpha-hydroxy acid)s and their associated copolymers:surface structure-biomedical function relationships;physicochemical strategies for surface modification; and, finally,synthetic strategies to increase biocompatibility for specific in-vivo and/or in-vitro biomedical applications.     

Optical molecular imaging for systems biology: from molecule to organism

The development of highly efficient analytical methods capable of probing biological systems at system level is an important task that is required in order to meet the requirements of the emerging field of systems biology. Optical molecular imaging (OMI) is a very powerful tool for studying the temporal and spatial dynamics of specific biomolecules and their interactions in real time in vivo. In this article, recent advances in OMI are reviewed extensively, such as the development of molecular probes that make imaging brighter, more stable and more informative (e.g., FPs and semiconductor nanocrystals, also referred to as quantum dots), the development of imaging approaches that provide higher resolution and greater tissue penetration, and applications for measuring biological events from molecule to organism level, including gene expression, protein and subcellular compartment localization, protein activation and interaction, and low-mass molecule dynamics. These advances are of great significance in the field of biological science and could also be applied to disease diagnosis and pharmaceutical screening. Further developments in OMI for systems biology are also proposed.     

New approach for chiral separation: from polysaccharide-based materials to chirality-responsive polymers

Chiral separation that is closely related to daily life is a meaningful research. Polysaccharide-(e.g., cellulose, amylose derivatives) based chiral packing materials afford powerful chiral stationary phases(CSPs) toward a broad range of racemic compounds. However, considering the explosive growth of specific chiral drugs, the separation efficiencies of these CSPs need further improvement, which calls for new approaches and strategies. Smart polymers can change their physical or chemical properties dynamically and reversibly according to the external stimuli(e.g., thermo-, pH, solvent, ion, light, critical parameters for chromatographic separation) exerted on them, subsequently resulting in tunable changes in the macroscopic properties of materials. In addition to their excellent controllability, the introduction of chiral characteristics into the backbones or side-chains of smart polymers provides a promising route to realize reversibly conformational transition in response to the chiral analytes. This dramatic transition may significantly improve the performance of materials in chiral separation through modulating the enantioselective interactions between materials and analytes. With the help of chirality-responsive polymers, intelligent and switchable CSPs could be developed and applied in column-liquid chromatography. In these systems, the elution order or enantioselectivity of chiral drugs can be precisely modulated, which will help to solve many challenging problems that involve complicated enantiomers. In this paper we introduce some typical examples of smart polymers that serve as the basis for a discussion of emerging developments of CPSs, and then briefly outline the recent CSPs based on natural and certain synthetic polymers.     

A Versatile Dynamic Mussel‐Inspired Biointerface: From Specific Cell Behavior Modulation to Selective Cell Isolation

Reported here is a novel dynamic biointerface based on reversible catechol‐boronate chemistry. Biomimetically designed peptides with a catechol‐containing sequence and a cell‐binding sequence at each end were initially obtained. The mussel‐inspired peptides were then reversibly bound to a phenylboronic acid (PBA) containing polymer‐grafted substrate through sugar‐responsive catechol‐boronate interactions. The resultant biointerface is thus capable of dynamic presentation of the bioactivity (i.e. the cell‐binding sequence) by virtue of changing sugar concentrations in the system (similar to human glycemic volatility). In addition, the sugar‐responsive biointerface enables not only dynamic modulation of stem cell adhesion behaviors but also selective isolation of tumor cells. Considering the highly biomimetic nature and biological stimuli‐responsiveness, this mussel‐inspired dynamic biointerface holds great promise in both fundamental cell biology research and advanced medical applications.     

Dendritic supermolecules--towards controllable nanomaterials

Dendritic molecules constitute one of the most exciting areas of modern nanochemistry, largely as a consequence of the unique properties associated with their branched architectures. This article describes how 'dendritic function' can also be achieved using small, synthetically accessible branched building blocks (individual dendrons) which simply self-assemble via non-covalent interactions to generate dendritic nanoscale architectures with novel behaviour. (a) Using non-covalent interactions at the focal point of a dendron allows the self-assembly of nanometre-sized supramolecular dendrimers around an appropriate template species. Such systems have potential applications in the controlled encapsulation and release of active ingredients. (b) Employing non-covalent intermolecular dendron-dendron interactions can give rise to the hierarchical assembly of nanostructured materials. Such assemblies of dendritic molecules ultimately express their molecular scale information on a macroscopic scale, and therefore have applications in materials science, for example as gels. (c) The multiple surface groups of dendrons are capable of forming multiple interactions with large surfaces, such as those found on biomolecules or in biological systems. Employing multivalent interactions between dendron surfaces and biological molecules opens up the potential application of dendritic systems as medicinal therapies. In summary, dendritic supermolecules offer a potentially cost-effective approach to the future application of dendritic systems to a range of real-world problems.     

Molecularly imprinted polymer based enantioselective sensing devices: A review

Chiral recognition is the fundamental property of many biological molecules and is a quite important field in pharmaceutical analysis because of the pharmacologically different activities of enantiomers in living systems. Enantio-differentiating signal of the sensor requires specific interaction between the chiral compounds (one or a mixture of enantiomers) in question and the selector. This type of interaction is controlled normally by at least three binding centers, whose mutual arrangement and interacting characteristics with one of the enantiomers effectively control the selectivity of recognition. Molecular imprinting technology provides a unique opportunity for the creation of three-dimensional cavities with tailored recognition properties. Over the past decade, this field has expanded considerably across the variety of disciplines, leading to novel transduction approaches and many potential applications. The state-of-art of molecularly imprinted polymer-based chiral recognition might set an exotic trend toward the development of chiral sensors. The objective of this review is to provide comprehensive knowledge and information to all researchers who are interested in exploiting molecular imprinting technology toward the rational design of chiral sensors operating on different transduction principles, ranging from electrochemical to piezoelectric, being used for the detection of chiral compounds as they pose significant impact on the understanding of the origin of life and all processes that occur in living organisms.     

Zwitterionic Polydopamine Engineered Interface for In Vivo Sensing with High Biocompatibility

Electrochemical sensing performance is often compromised by electrode biofouling (e.g., proteins nonspecific binding) in complex biological fluids; however, the design and construction of a robust biointerface remains a great challenge. Herein, inspired by nature, we demonstrate a robust polydopamine-engineered biointerfacing, to tailing zwitterionic molecules (i.e., sulfobetaine methacrylate, SBMA) through Michael Addition. The SBMA-PDA biointerface can resist proteins nonspecific binding in complex biological fluids while enhancing interfacial electron transfer and electrochemical stability of the electrode. In addition, this sensing interface can be integrated with tissue-implantable electrode for in vivo analysis with improved sensing performance, preserving ca. 92.0% of the initial sensitivity after 2 h of implantation in brain tissue, showing low acute neuroinflammatory responses and good stability both in normal and in Parkinson′s disease (PD) rat brain tissue.     

Conformational selectivity of peptides for single-walled carbon nanotubes

Carbon nanotubes show promising prospects for applications ranging from molecular electronics to ultrasensitive biosensors. An important aspect to understanding carbon nanotube properties is their interactions with biomolecules such as peptides and proteins, as these interactions are important in our understanding of nanotube interactions with the environment, their use in cellular systems, as well as their interface with biological materials for medical and diagnostic applications. Here we report the sequence and conformational requirements of peptides for high-affinity binding to single-walled carbon nanotubes (SWNTs). A new motif, X(1)THX(2)X(3)PWTX(4), where X(1) is G or H, X(2) is H or D or null, X(3) is null or R, and X4 is null or K, was identified from two classes of phage-displayed peptide libraries. The high affinity binding of the motif to SWNTs required constrained conformations which were achieved through either the extension of the amino acid sequence (e.g., LLADTTHHRPWT) or the addition of a constrained disulfide bond (e.g., CGHPWTKC). This motif shows specific high-affinity to the currently studied SWNTs, compared to previously reported peptides. The conformations of the identified peptides in complex with SWNTs were also characterized with a variety of biophysical methodologies including CD, fluorescence, NMR spectroscopy, and molecular modeling.     

Dispersions based on noble metal nanoparticles-DNA conjugates

Many biomolecules have specific binding properties in the nanostructure formation; they are attractive materials for nanotechnology. One such promising construction material for growing a well-defined nanostructure is deoxyribonucleic acid, due to its π-electron hydrophobic core and predictable recognition attributed to the specificity of Watson–Crick base-pairing. Hydrogen bonding provides the specificity behind the matching of complementary pairs of single-stranded (ss) DNA to hybridize into a double strand (ds) of helical DNA. The double-helical structure of DNA is determined by a subtle balance of noncovalent interactions among the DNA building blocks. The most prominent role is played by the interactions between the DNA bases, where two binding motifs can be recognized: planar hydrogen bonding and vertical stacking. DNA-based nanotechnology has generated interest in a number of applications due to the specificity, programmability, and reproducibility of DNA interaction with noble metal nanoparticles. 5′ and 3′ thiol moieties are used to prepare composite DNAs, DNA–gold nanoparticle conjugates and nanostructures with a variety of nanoparticle-based DNA assays. Particularly, color changes induced by the association of nanometer-sized gold particles provide a basis of a simple yet highly selective method for detecting specific biological reactions between anchored ligand molecules and receptor molecules in the milieu. Colloidal noble metal nanoparticles, in particular, have found application in a variety of assay formats in which analyte binding is coupled to particle adsorption. The extreme sensitivity of the bandwidth, the peak height, and the position of the absorption (or scattering) maximum of surface plasmon resonance spectra to environmental changes have prompted the development of approaches directly monitor the DNA hybridization. The same features that make DNA an effective molecule for the storage of genetic information also render it useful as an engineering material for the construction of smart objects at the nanometer scale because of its ability to self organize into desired structures via the specific hybridization of complementary sequences. Biocompatibility between gold nanomaterials and biological scaffolding is crucial to the development of smart biomaterials. These DNA/metal colloids are interesting for their fundamental properties as well as for applications in nanomaterials science and nanobiotechnology.     

Bioconjugated Luminescent Nanoparticles for Biological Applications

Abstract

Inorganic nanostructures that interface with biological systems have recently attracted widespread interest in biology and medicine. Nanoparticles are thought to have potential as novel luminescent probes for both diagnostic (e.g., imaging) and therapeutic (e.g., drug delivery) purposes because of their size comparable to biomolecules and their novel optical, electronic, and magnetic properties. Critical issues for successful nanoparticle delivery include the ability to target specific tissues and cell types and escape from the biological particulate filter known as reticuloendothelial system. Three distinct types of luminescent nanoparticles have been identified which show promise in bioanalysis, namely dye‐doped nanoparticles, semiconductor and metal nanoparticles. In this article we examine the recent advances in the development of dye‐doped nanoparticles, metal and semiconductor nanoparticles, bioconjugation schemes to attach these nanoparticles to biomolecules and a few biological applications.     

Biomimetic click assembled multilayer coatings exhibiting responsive properties

Stimuli-responsive polymers are capable of changing their physico-chemical properties in a dynamic way, to respond to variations on the surrounding environment. These materials have gained increasingly importance for different areas, such as drug delivery, biosensors, microelectronic systems and also for the design and modification of biomaterials to apply on tissue engineering field. In the last years, different strategies have been envisaged for the development of stimuli-responsive biomaterials. Layer-by-layer (LbL) is a promising and versatile technique to modify biomaterials' surfaces, and has allowed tailoring interactions with cells. In this study, LbL is used to construct biomimetic stimuli-responsive coatings using elastin-like recombinamers (ELRs). The recombinant nature of ELRs provides the ability to introduce specific bioactive sequences and to tune their physicochemical properties, making them attractive for biomedical and biological applications. By using complementary clickable ELRs, we were able to construct multilayer coatings stabilized by covalent bonds, resulting from the Huisgen 1,3-dipolar cycloaddition of azides and alkynes. Herein, we exploited the switchable properties of the ELRs-based coatings which are dependent on lower critical solution temperature (LCST) transition. Above LCST, the polymers collapsed and nanostructured precipitates were observed on the surface's morphology, increasing the water contact angle. Also, the influence of pH on prompting reversible responses on coatings was evaluated. Finally, in vitro cell studies using a C2C12 myoblastic cell line were performed to perceive the importance of having bioactive domains within these coatings. The effect of RGD incorporation is clearly noted not only in terms of adhesion and proliferation but also in terms of myoblast differentiation.