Periodic Reporting for period 2 - CATCH (Synthetic Catch Bonds)
Reporting period: 2023-01-01 to 2024-06-30
This project aims to study naturally occurring catch bonds, molecular links with unique mechanical properties, and realize the first artificial equivalents using supramolecular mechanochemistry. This study revolves around the following objectives:
* a detailed exploration of the molecular mechanisms by which biological catch bonds function (e.g. how is a force-induced conformational switch encoded in their chemical design and macromolecular architecture)
* the establishment of novel tools to probe the molecular mechanics of catch bonds both at the scale of single molecules and catch bond collectives in materials
* the design and synthesis of artificial catch bonds
* the preparation and study of catch bonded materials
* the development of theoretical frameworks to describe and predict catch bond function, at the molecular and material scale.
* using mechanically engineered materials to promote in-vitro cell culture
Catch bonds are a crucial design element used by Nature to build smart and mechanically-aware materials: they play a crucial role in a wide array of biological processes, ranging from cell adhesion in tissues, bacterial adhesion in biofilms, mechanical communication between cells, blood clotting, mechanotransduction and cell division. To date, these design elements have remained exlusive to nature as there were no strategies to make molecular designs in a synthetic laboratory to emulate their mechanical response. As a result, a crucial biological design strategy to make materials that can perceive and actively adapt to mechanical stimuli remained beyond reach for bio-mimetic materials. We anticipate that the successful completion of this project will bring catch bonds to the toolbox of the material scientists, e.g. to create mechano-adaptive gels for soft robotics, as a means to tailor mechanical communications between cells in tissue engineering and to create novel bio-inspired hydrogels which are resilient to mechanical damage. Achieving this goal faces several challenges around which this project is centered, including how to design a unique molecular mechanotype from scratch, how to quantify catch bonds in a high-throughput fashion, for which a new method was designed and implemented (see image FFS.png) how to probe mechanical patterns in (catch) bonded materials and how to design materials, based on these principles, to promote cell culture and proliferation.
* a detailed exploration of the molecular mechanisms by which biological catch bonds function (e.g. how is a force-induced conformational switch encoded in their chemical design and macromolecular architecture)
* the establishment of novel tools to probe the molecular mechanics of catch bonds both at the scale of single molecules and catch bond collectives in materials
* the design and synthesis of artificial catch bonds
* the preparation and study of catch bonded materials
* the development of theoretical frameworks to describe and predict catch bond function, at the molecular and material scale.
* using mechanically engineered materials to promote in-vitro cell culture
Catch bonds are a crucial design element used by Nature to build smart and mechanically-aware materials: they play a crucial role in a wide array of biological processes, ranging from cell adhesion in tissues, bacterial adhesion in biofilms, mechanical communication between cells, blood clotting, mechanotransduction and cell division. To date, these design elements have remained exlusive to nature as there were no strategies to make molecular designs in a synthetic laboratory to emulate their mechanical response. As a result, a crucial biological design strategy to make materials that can perceive and actively adapt to mechanical stimuli remained beyond reach for bio-mimetic materials. We anticipate that the successful completion of this project will bring catch bonds to the toolbox of the material scientists, e.g. to create mechano-adaptive gels for soft robotics, as a means to tailor mechanical communications between cells in tissue engineering and to create novel bio-inspired hydrogels which are resilient to mechanical damage. Achieving this goal faces several challenges around which this project is centered, including how to design a unique molecular mechanotype from scratch, how to quantify catch bonds in a high-throughput fashion, for which a new method was designed and implemented (see image FFS.png) how to probe mechanical patterns in (catch) bonded materials and how to design materials, based on these principles, to promote cell culture and proliferation.
Project update (01-02-2022): The action was commenced in this reporting period 1. Project start proceeded without delays or problems. Personnel was successfully recruited, albeit with somewhat delayed starting dates than anticipated due to COVID-related delays in the conclusion of their prior studies. Scientific progress has been good: efforts have been focussed in three major topics: i) establishing a rapid mechanotyping method to identify and characterize molecular catch bonds, this has been successful, reaching the first milestone of the project, and a publication is currently in preparation and will be submitted in the weeks following submission of this report, ii) design and study of DNA based synthetic catch bonds, one of the main aims of the project, also here progress is good and first proof has emerged that a first synthetic catch bond has been made, a major publication is anticipated in the coming month, iii) study of covalent synthetic catch bonds, in collaboration with planned collaborator, has proceeded faster than expected and seems to reach a successful first conclusion also in the coming months. In addition to these main topics, we have begun preparatory work for planned cell culture experiments, to explore material-control over cell division and proliferation, ahead of schedule due to the local availability of new expertise through novel collaborations. So far, no major problems have occurred in the execution of the scientific and financial progress of this action.
To date, artificial catch bonds have not been realised; this project aims to do so and thus extends beyond the state-of-the-art. Expected results until the end of the project are:
* the first report of artificial catch bonds
* a deeper mechanistic understanding of how catch bond is chemically encoded in molecular designs
* the first realisation of catch bonded hydrogels
* a detailed study of catch bond mechanics in hydrogels
* the establishment of novel tools for molecular mechanotyping and mechanical reporting in hydrogels and biopolymer networks
* novel theoretical framework to describe catch bonds from the molecular to the material scale
* New hydrogel technologies for cell culture
* the first report of artificial catch bonds
* a deeper mechanistic understanding of how catch bond is chemically encoded in molecular designs
* the first realisation of catch bonded hydrogels
* a detailed study of catch bond mechanics in hydrogels
* the establishment of novel tools for molecular mechanotyping and mechanical reporting in hydrogels and biopolymer networks
* novel theoretical framework to describe catch bonds from the molecular to the material scale
* New hydrogel technologies for cell culture