Understanding and Reconstructing Biointerfaces with 3D Soft Nanolithography

3 - 5 July 2019, London, United Kingdom


Introduction
In studying biological interfaces where carbohydrates are prevalent – such as the glycocalyx or extracellular matrix – scientists are only beginning to investigate how chemical composition, binding thermodynamics, and 3D structure work synergistically to control development, communication, and disease progression. Carbohydrate-binding – in contrast to other biomolecule-substrate recognition – is dependent sensitively upon valency, glycan-glycan spacing, and other aspects of 3D morphology, and is therefore far less understood than other types of biological interactions. Synthetic analogues of these materials could result in new scaffolds for tissue engineering, biological arrays for interrogating disease, and a more complete picture of how interfacial carbohydrate recognition is dependent upon 3D nanoscale morphology. Thus the importance of reproducing the 3D structure of carbohydrate interfaces for understanding their physical and biological properties cannot be overstated. Advances in this critical area of chemistry, however, have been slow because of unresolved challenges related to controlling the 3D structure of matter at the biological length scale and the lack of understanding how interfacial carbohydrate composition and structure affects physical properties and, in turn, biological function.
 
Capturing the interfacial dynamics that drive the mechanical and biological properties of natural carbohydrate-based nanomaterials will require synergistic advances in 3D nanolithography, surface characterization, and organic and macromolecular chemistry at interfaces. The challenge, and the reason why this topic merits a Faraday Discussion, is that many of the researchers working in this area come from disparate fields that rarely if ever communicate, including physical chemistry, surface chemistry, mechanical engineering, biology, and material science. Biological interfaces are often composed entirely of layers of carbohydrates and their unique binding dynamics involve multivalent and cooperative interfacial interactions that can only be mimicked by dense, 3D reproductions of the natural counterparts. Thus glycochemistry and 3D printing should be closely linked in an effort to study and reproduce the properties of carbohydrate-containing biomaterials and biointerfaces, but the idiosyncratic nature and inherent difficulty of carbohydrate chemistry has delayed the reproduction of cell-surface mimics at the molecular level.

Format

The Faraday Division have been organising high impact Faraday Discussions in rapidly developing areas of the physical sciences, with a focus on physical chemistry and its interfaces with other scientific disciplines for over 100 years. Faraday Discussions have a special format where research papers written by the speakers are distributed to all participants before the meeting, and most of the meeting is devoted to discussing the papers. Everyone contributes to the discussion - including presenting their own relevant research. The research papers and a record of the discussion are published in the journal Faraday Discussions.

Find out more about the Faraday Discussions in this video

Aims

Recently, groups from different fields have been making significant advances in creating the printing tools, chemical reactions, and analytical approaches for developing and studying 3D nanostructures composed of glycans and glycomimetics. This Faraday Discussion aims to bring these communities together in a single symposium to create a new language for approaching the challenge of carbohydrate-based biointerfaces ranging from researchers who focus entirely on printing tools, surface chemistry, binding thermodynamics, and glycobiology, and others whose nascent efforts to combine these are leading to groundbreaking new materials and a revolutionary understanding of these unconventional surface interactions, where multivalency and cooperativity have an outsized role. This symposium will show how chemistry, particularly the combination of physical and organic chemistry, will continue to drive advances in the field, and provide new approaches to understanding, and in turn, creating biomimetic materials with precisely controlled nanoscale structure in three dimensions.

Themes

  • Multidimensional Micro- and Nano-printing Technologies
Biological interfaces are complex, three dimensional, and span several orders of magnitude in critical dimensions. Studying them, therefore, requires new tools that operate at the nano- and micro-scale, and that are non-destructive towards the delicate organic and biological materials that dominate biointerfaces. The particular challenges in this field are that the instrumentation capable of creating objects with nanoscale dimensions require high-energy inputs and are therefore incompatible with the soft materials that comprise cellular interfaces. Researchers seeking to understand and reconstruct biological interfaces overcome this limitation with new soft-matter compatible nanofabrication tools. This session will focus on developments in nanoprinting and nanofabrication technologies that are used to immobilize delicate organic and biologically active molecules and interrogate their physical properties (e.g., the interaction of proteins with surfaces and the impacts on electronic structure, printing techniques to express biological mimics at surfaces and nano/micro objects that interact with and are taken up by living cells).
  • Preparation of Multivalent Glycan Micro- and Nano-Arrays
Recreating the binding thermodynamics that are prevalent on biointerfaces requires scaffolds that capture multivalent and cooperative ligand presentation. The complexity of carbohydrate synthesis and their difficult isolation from natural sources precludes their facile deployment in glycan micro- and nano-arrays. To this end, different schools of thought are emerging on how to capture this presentation. Speakers in this session represent two increasingly popular approaches where either multivalent biological scaffolds are used as anchors for native glycans or where glycomimetic polymers are printed or grown from surfaces. This session will focus on how the different approaches alter the binding and mechanical properties of the resulting substrates.
  • Glycan Interactions on Glycocalyx Mimetic Surfaces
Binding at biological interfaces, which is dominated by carbohydrate recognition, is controlled by weak interactions, where multivalency and cooperativity have an outsized role in determining selectivity and specificity. New physical models and data are needed to understand how these binding modes drive hierarchical biological processes, but these efforts are limited by the dearth of materials that model the chemical composition and structural complexity of the layers of glycans coating eukaryotic cells. Speakers in this session will come from groups who are studying glycan-substrate recognition on biomimetic surfaces using a variety of spectroscopic probes and showing how these data can lead to new thermodynamic models that can explain exotic biological behaviour.
  • New Directions in Surface Functionalization and Characterization
Surfaces – such as glass, metal, nitrocellulose, polymeric, or other reactive substrates – modified with organic compounds have, for decades, been used to control macroscopic interfacial properties (e.g., wetting, anti-fouling, etc.) but advances in synthesis, physical-organic chemistry and spectroscopy of soft-matter functionalized surfaces enable the tailoring of surface interactions at the molecular scale that affect interactions with biological molecules either directly (naked biopolymers) or via expression at a cell membrane. Specifically, when these substrates are functionalized with patterns of organic and biologically-active molecules, the physical properties and biological responses can be manipulated. As such, the ability to understand and recreate biological interfaces is advanced directly by new chemistries for immobilizing soft-matter onto surfaces. This session will focus on new developments in the functionalization of surfaces that takes place at the nexus of physical, organic, and biochemistry for the purpose of understanding and controlling the properties of biological molecules at interfaces from specific, molecular interactions to complex biological functions such as cell differentiation and morphology. Speakers in this session will present efforts to use new biocompatible chemistries to functionalize surfaces, with an emphasis on the quantitative investigation of reaction kinetics and mechanisms at interfaces.
Venue
The Royal Society of Chemistry

The Royal Society of Chemistry, Burlington House, Piccadilly, London, W1J 0BA, United Kingdom

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