Recently, there has been an outburst of research on engineered cell-material interfaces driven by nanotechnology and its tools and techniques. This tutorial review begins by providing a brief ...introduction to nanostructured materials, followed by an overview of the wealth of nanoscale fabrication and analysis tools available for their development. This background serves as the basis for a discussion of early breakthroughs and recent key developments in the endeavour to develop nanostructured materials as smart interfaces for fundamental cellular studies, tissue engineering and regenerative medicine. The review covers three major aspects of nanostructured interfaces - nanotopographical control, dynamic behaviour and intracellular manipulation and sensing - where efforts are continuously being made to further understand cell function and provide new ways to control cell behaviour. A critical reflection of the current status and future challenges are discussed as a conclusion to the review.
Nanostructured materials can be used as smart interfaces to further understand and control the complex interplay of events and interactions occurring within living cells.
The development of surfaces that have switchable properties, also known as smart surfaces, have been actively pursued in the past few years. The recent surge of interest in these switchable systems ...stems from the widespread number of applications to many areas in science and technology ranging from environmental cleanup to data storage, micro- and nanofluidic devices. Moreover, the ability to modulate biomolecule activity, protein immobilisation, and cell adhesion at the liquid-solid interface is important in a variety of biological and medical applications, including biofouling, chromatography, cell culture, regenerative medicine and tissue engineering. Different materials have been exploited to induce such changes in surface biological properties that are mostly based on self-assembled monolayers or polymer films. This critical review focuses on the recent progress in the preparation of these switchable surfaces, and highlights their applications in biological environments. The review is organized according to the external stimuli used to manipulate the properties of the substrate-chemical/biochemical, thermal, electric and optical stimuli. Current and future challenges in the field of smart biological surfaces are addressed (189 references).
Label-free protein characterization at surfaces is commonly achieved using digestion and/or matrix application prior to mass spectrometry. We report the assignment of undigested proteins at surfaces ...in situ using secondary ion mass spectrometry (SIMS). Ballistic fragmentation of proteins induced by a gas cluster ion beam (GCIB) leads to peptide cleavage producing fragments for subsequent Orbitrap
analysis. In this work we annotate 16 example proteins (up to 272 kDa) by de novo peptide sequencing and illustrate the advantages of this approach by characterizing a protein monolayer biochip and the depth distribution of proteins in human skin.
Chimeric antigen receptor (CAR)-T cells are emerging as a generation-defining therapeutic however their manufacture remains a major barrier to meeting increased market demand. Monitoring critical ...quality attributes (CQAs) and critical process parameters (CPPs) during manufacture would vastly enrich acquired information related to the process and product, providing feedback to enable real-time decision making. Here we identify specific CAR-T cytokines as value-adding analytes and discuss their roles as plausible CPPs and CQAs. High sensitivity sensing technologies which can be easily integrated into manufacture workflows are essential to implement real-time monitoring of these cytokines. We therefore present biosensors as enabling technologies and evaluate recent advancements in cytokine detection in cell cultures, offering promising translatability to CAR-T biomanufacture. Finally, we outline emerging sensing technologies with future promise, and provide an overall outlook on existing gaps to implementation and the optimal sensing platform to enable cytokine monitoring in CAR-T biomanufacture.
Sialic acid recognition remains an interesting and challenging target in molecular receptor design. Herein, we report a series of benzoboroxole-based receptors in which cationic hydrogen-bond donors ...have been introduced and shown to promote multipoint sialic acid recognition. One striking feature revealed by these receptors is that the carboxylate sialic acid residue is the primary binding determinant for recognition by benzoboroxole, in which the presence of charge-reinforced hydrogen bonds results in enhanced selectivity for sialic acid over other carbohydrates and a 4.5-fold increase in affinity. These findings open up wide possibilities for benzoboroxole-based receptors use in life science research, biotechnology, and diagnostics.
Glycans - simple or complex carbohydrates - play key roles as recognition determinants and modulators of numerous physiological and pathological processes. Thus, many biotechnological, diagnostic and ...therapeutic opportunities abound for molecular recognition entities that can bind glycans with high selectivity and affinity. This review begins with an overview of the current biologically and synthetically derived glycan-binding scaffolds that include antibodies, lectins, aptamers and boronic acid-based entities. It is followed by a more detailed discussion on various aspects of their generation, structure and recognition properties. It serves as the basis for highlighting recent key developments and technical challenges that must be overcome in order to fully deal with the specific recognition of a highly diverse and complex range of glycan structures.
Development of natural and artificial receptors with high affinity and exquisite specificity for various purposes remains an important goal and challenge.
The molecular recognition of saccharides by synthetic hosts has become an appealing but elusive task in the last decades. Herein, we combine Dynamic Combinatorial Chemistry (DCC) for the rapid ...self-assembly and screening of virtual libraries of receptors, with the use of ITC and NMR to validate the hits and molecular modelling to understand the binding mechanisms. We discovered a minimalistic receptor, 1F (
-benzyl-L-phenylalanine), with considerable affinity for fructose (
= 1762 M
) and remarkable selectivity (>50-fold) over other common monosaccharides. The approach accelerates the discovery process of receptors for saccharides.
Studies report that intense physical activity influences the down-regulation of immune function in athletes as well as the interaction between adipose tissue and the immune system. This study aimed ...to compare the plasma soluble levels of the immune checkpoint HLA-G (sHLA-G) molecule with the fat mass and muscle mass index among 77 bodybuilders and 64 controls. The comparisons of the percentage of body fat (%BF) revealed that the groups of male and female bodybuilders showed a statistically significant reduction in the percentage of body fat when compared to their control group, (P <0.0001, for both comparisons). Regarding sHLA-G levels, the comparisons showed that the group of male bodybuilders had significantly higher sHLA-G levels compared to the group of female bodybuilders (P = 0.0011). Our results showed that in bodybuilders with less body fat, the systemic levels of soluble HLA-G, an immunological molecule with recognized immunosuppressive function, are significantly higher and suggest that this immune mechanism may corroborate the immunosuppressive state in athletes undergoing intense and prolonged physical training.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In nature, interfacial molecular interactions are at the heart of all biological processes and are mediated by diverse stimuli. Inspired by nature's responsive mechanisms and our increased capability ...to manipulate matter at the molecular level, new bio-interface materials are being developed that respond efficiently to a variety of external stimuli. In this Review, we discuss emerging methods for imparting surfaces with dynamic properties and how this, in turn, is leading to increased functional complexity at the bio-interface. We examine how recent advances are becoming important in providing new insights into cell behaviour and spurring substantial progress in the fields of regenerative medicine and tissue engineering. These advances provide new opportunities to address the complex issues associated with biofouling and facilitate the production of implantable on-demand sensing devices and highly effective delivery, bioseparation and bioelectrocatalytic systems. Although progress is being made, we also highlight that current methods are still limited in their capability to impart complex functionality onto the bio-interface to fully address the current challenges in biotechnology and biomedicine. Exciting prospects include the incorporation of full reversibility of interactions, a broad repertoire of multi-responsiveness and bidirectional actuation at the bio-interface, as well as the capability to incorporate the developed systems in practical applications.Bio-interface materials inspired by natural systems that respond efficiently to various external stimuli can dynamically regulate molecular interactions between biological entities and material surfaces. In this Review, Gomes and colleagues describe advances in bio-interface materials that may provide insights into cell behaviour, biofouling and the production of on-demand devices with medical applications, among others.
Recognition of oligosaccharides is associated with very limited specificity due to their strong solvation in water and the high degree of subtle structural variations between them. Here, ...oligosaccharide recognition sites are created on material surfaces with unmatched, binary on–off binding behavior, sharply discriminating a target oligosaccharide over closely related carbohydrate structures. The basis for the superselective binding behavior relies on the highly efficient generation of a pure, high order complex of the oligosaccharide target with synthetic carbohydrate receptor sites, in which the spatial arrangement of the multiple receptors in the complex is preserved upon material surface incorporation. The synthetic binding scaffolds can easily be tailored to recognize different oligosaccharides and glycoconjugates, opening up a realm of possibilities for their use in a wide field of applications, ranging from life sciences to diagnostics.
A unique modular, synthetic strategy allows for the creation of artificial binding sites with precise spatial positioning of multiple carbohydrate receptors, enabling the remarkable ability to distinguish a target oligosaccharide over closely related carbohydrate structures. The synthetic binding scaffolds can easily be tailored to bind not only specifically oligosaccharides in free form but also when they are linked to proteins as glycoconjugates.