Periodic Reporting for period 1 - Nano Traction (Nano Traction)
Periodo di rendicontazione: 2018-03-01 al 2020-02-29
Nano- and microscale chemical traction such as that observed in the motion of myosin along actin filaments play a pivotal role in the directed motion of molecules and other larger structures within the cell. This motive force is fundamental to processes such as mitosis, cellular motion and muscle contraction. Yet, despite intense research into the mechanisms that underpin it there are currently no artificial analogues that can replicate its strength and utility at the nanometer and micrometre length scales. This fellowship sought to address this by creating nano- and microparticles that autonomously move across a surface directed by chemical gradients.
To achieve this a new system of particle traction was devised that exploits the precise and adaptive nature of disulphide bonds (i.e. covalent bonds between two sulphur atoms) between particles and surfaces. The hypothesis that drives this work is that stimuli that affected the rate and equilibrium position of the bond-forming reactions, if applied asymmetrically around the particle, would cause it to move across the surface. Disulphide bonds were chosen as the dynamic covalent bond for this system because the stimuli that affect their equilibrium include the presence of oxidants or reductants. Such stimuli can be created by electrodes, offering the possibility of electrical control of particle motion. They are also present inside and outside of cells meaning this method of particle traction can be reconfigured to work with enzymes that catalyse disulphide exchange in life-like environments. The ultimate aims of this work are to use these motile particle systems to create electrically driven artificial micro muscles and to use them to probe and map the redox environment around cells, particularly those in diseased tissues.
To achieve this a new system of particle traction was devised that exploits the precise and adaptive nature of disulphide bonds (i.e. covalent bonds between two sulphur atoms) between particles and surfaces. The hypothesis that drives this work is that stimuli that affected the rate and equilibrium position of the bond-forming reactions, if applied asymmetrically around the particle, would cause it to move across the surface. Disulphide bonds were chosen as the dynamic covalent bond for this system because the stimuli that affect their equilibrium include the presence of oxidants or reductants. Such stimuli can be created by electrodes, offering the possibility of electrical control of particle motion. They are also present inside and outside of cells meaning this method of particle traction can be reconfigured to work with enzymes that catalyse disulphide exchange in life-like environments. The ultimate aims of this work are to use these motile particle systems to create electrically driven artificial micro muscles and to use them to probe and map the redox environment around cells, particularly those in diseased tissues.
This project has been an exciting success. Thiol coated particles and surfaces were created and the dynamic nature of the covalent bonds to their surfaces probed. Detailed investigations found that strong non-specific binding interactions between the particles and the surface were present and elicited further detailed study. This produced fascinating insights into the physical parameters and chemical cues that control disulphide driven particle motion on a surface.
Following this, the system went through successive iterations focussed on isolating the individual contributions to the attractive forces (e.g. electrostatic interactions) between the particles and the surface and then reducing or removing them. Initially, studies concentrated on using a variety of small molecule-based linkers and both commercial and in-house prepared particles. To improve on this research advanced to creating a novel modular surface functionalisation system centred around surface tethered polymerisation. This forms the basis for a key new platform technology for the modification of both particle and surface properties that will allow the creation of new well defined dynamic covalent surfaces - crucial to the creation of adaptive biomaterials and particle-surface traction systems.
This highly interdisciplinary project was made possible by the world-leading expertise in biomaterials synthesis and characterization within the Stevens Group, as well as the synthesis and chemical characterization facilities at the Karolinska Institute (KI) and Science for Life (SciLife) Laboratories. The wealth of research experience within the Stevens Group provided excellent support for overcoming the synthetic and characterisation challenges faced during this project and allowed significant progress to be made toward the development of these fascinatingly intricate systems.
Following this, the system went through successive iterations focussed on isolating the individual contributions to the attractive forces (e.g. electrostatic interactions) between the particles and the surface and then reducing or removing them. Initially, studies concentrated on using a variety of small molecule-based linkers and both commercial and in-house prepared particles. To improve on this research advanced to creating a novel modular surface functionalisation system centred around surface tethered polymerisation. This forms the basis for a key new platform technology for the modification of both particle and surface properties that will allow the creation of new well defined dynamic covalent surfaces - crucial to the creation of adaptive biomaterials and particle-surface traction systems.
This highly interdisciplinary project was made possible by the world-leading expertise in biomaterials synthesis and characterization within the Stevens Group, as well as the synthesis and chemical characterization facilities at the Karolinska Institute (KI) and Science for Life (SciLife) Laboratories. The wealth of research experience within the Stevens Group provided excellent support for overcoming the synthetic and characterisation challenges faced during this project and allowed significant progress to be made toward the development of these fascinatingly intricate systems.
The results from this fellowship have advanced the state-of-the-art in the intersecting areas of supramolecular chemistry, nanoscience and bioengineering. The creation and study of these large dynamic covalent systems has never been achieved before and this work has provided a wealth of insight into them. The new synthetic tools developed during this project makes their design and creation inherently modular allowing additional functional groups to be introduced into them to tune and adapt the system.
Secondly, this project demonstrated a new method for the surface patterning of functional groups onto soft hydrogels using reversible disulphide chemistry. Following the initial success with his technology, it is currently under investigation in applications related to the creation of patterned biomaterials.
This project has thus established new methods for preparing stimuli-responsive macro-scale systems, which, it is hoped, will lead to new technologies in areas as diverse as artificial muscles and nanoparticle-based theranostics.
Secondly, this project demonstrated a new method for the surface patterning of functional groups onto soft hydrogels using reversible disulphide chemistry. Following the initial success with his technology, it is currently under investigation in applications related to the creation of patterned biomaterials.
This project has thus established new methods for preparing stimuli-responsive macro-scale systems, which, it is hoped, will lead to new technologies in areas as diverse as artificial muscles and nanoparticle-based theranostics.