Improving Cancer and Alzheimer’s Therapy by Better Understanding ‘Microtubules’ – railways in (almost) every cell in your body


Single microtubule ‘railway track’ surrounded by bubbles of ‘cargo’ held inside cells. Credit: University of Warwick

New work from the University of Warwick shows how a microscopic ‘railway’ system in our cells can optimise its structure to better suit bodies’

The work was conducted by Professor Robert Cross, director of the centre for mechanochemical cell biology at Warwick Medical School and leader of the Cross lab.

His team based at Warwick Medical School has been looking at how the microtubule ‘railway tracks’ inside cells are built. Almost every cell in our bodies contains a ‘railway’ network, a system of tiny tracks called microtubules that link important destinations inside the cell. Professor Cross’ team found the system of microtubule rails inside cells can adjust its own stability depending on whether it is being used or not..

Prof Cross said: “The microtubule tracks of the cellular railway are almost unimaginably small – just 25 nanometres across (a nanometre being a millionth of a millimetre).The railway is just as crucial to a well-run cell as a full-size railway is to a well-run country. For cells and for countries the problem is very much the same – how to run a better railway?”

“Imagine if the tracks of a real railway were able to ask themselves, ‘am I useful?’ To find out, they would check how often a railway engine passed along them.

“It turns out that the microtubule railway tracks inside cells can do exactly that – they check whether or not they are in contact with tiny railway engines (called kinesins). If they are, then they remain stably in place. If they are not, they disassemble themselves. We think this allows the sections of microtubule rail to be recycled to build new and more useful rails elsewhere in the cell.”

The paper, ‘Kinesin expands and stabilizes the GDP-microtubule lattice’ published (12 March 2018) in Nature Nanotechnology, shows that when the kinesin railway engines contact their microtubule rails, they subtly change their structure, producing a very slight lengthening that stabilises the rail.

Using a custom built microscope, the Warwick Open Source Microscope, the researchers who are also based at Warwick Systems Biology Centre and Mathematics Institute, University of Warwick, detected a 1.6% increase in the length of microtubules attached to kinesins, with a 200 times increase in their lifetime.

By revealing how microtubules are stabilised and destabilised, the team hope to throw new light on the workings of a number of human diseases (for example Alzheimer’s), which is linked to abnormalities in microtubule function. They are hopeful also that their work may ultimately lead to improved cancer therapy because the railway is so vital (for example for cell division), as its microtubule tracks are a key target for cancer drugs such as Taxol. Exactly how Taxol stabilises microtubules in cells remains poorly understood.

Professor Cross added: “Our new work shows that the kinesin railway engines stabilise microtubules in a Taxol-like way. We need to understand as much as we can about how microtubules can be stabilised and destabilised, to pave and illuminate the road to improved therapies.”

More information: Daniel R. Peet et al, Kinesin expands and stabilizes the GDP-microtubule lattice, Nature Nanotechnology (2018). DOI: 10.1038/s41565-018-0084-4

Provided by: University of Warwick

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Breakthrough in ‘wonder’ materials paves way for flexible tech


breakthrough-2d-structures

Credit: University of Warwick

 

Gadgets are set to become flexible, highly efficient and much smaller, following a breakthrough in measuring two-dimensional ‘wonder’ materials by the University of Warwick.

Dr Neil Wilson in the Department of Physics has developed a new technique to measure the electronic structures of stacks of two-dimensional materials – flat, atomically thin, highly conductive, and extremely strong materials – for the first time.

Multiple stacked layers of 2-D materials – known as heterostructures – create highly efficient optoelectronic devices with ultrafast electrical charge, which can be used in nano-circuits, and are stronger than materials used in traditional circuits.

Various heterostructures have been created using different 2-D materials – and stacking different combinations of 2-D materials creates new with new properties.

Dr Wilson’s technique measures the electronic properties of each layer in a stack, allowing researchers to establish the optimal structure for the fastest, most efficient transfer of electrical energy.

The technique uses the photoelectric effect to directly measure the momentum of electrons within each layer and shows how this changes when the layers are combined.

The ability to understand and quantify how 2-D material heterostructures work – and to create optimal semiconductor structures – paves the way for the development of highly efficient nano-circuitry, and smaller, flexible, more wearable gadgets.

Solar power could also be revolutionised with heterostructures, as the atomically thin layers allow for strong absorption and efficient power conversion with a minimal amount of photovoltaic material.

Dr Wilson comments on the work: “It is extremely exciting to be able to see, for the first time, how interactions between atomically thin layers change their electronic structure. This work also demonstrates the importance of an international approach to research; we would not have been able to achieve this outcome without our colleagues in the USA and Italy.”

Dr Wilson worked formulated the technique in collaboration with colleagues in the theory groups at the University of Warwick and University of Cambridge, at the University of Washington in Seattle, and the Elettra Light Source, near Trieste in Italy.

Understanding how interactions between the atomic layers change their required the help of computational models developed by Dr Nick Hine, also from Warwick’s Department of Physics.

Explore further: Model accurately predicts the electronic properties of a combination of 2-D semiconductors

More information: Neil R. Wilson et al. Determination of band offsets, hybridization, and exciton binding in 2D semiconductor heterostructures, Science Advances (2017). DOI: 10.1126/sciadv.1601832

 

Tiny ‘Lego’ blocks Build Janus nanotubes: For NEW drugs and water purification


Nanotubes images(Nanowerk News) Researchers have created tiny protein  tubes named after the Roman god Janus which may offer a new way to accurately  channel drugs into the body’s cells.
Using a process which they liken to molecular Lego, scientists  from the University of Warwick and the University of Sydney have created what  they have named ‘Janus nanotubes’ – very small tubes with two distinct faces.  The study is published in the journal Nature Communications (“Janus cyclic peptide–polymer nanotubes”).
They are named after the Roman god Janus who is usually depicted  as having two faces, since he looks to the future and the past.
The Janus nanotubes have a tubular structure based on the  stacking of cyclic peptides, which provide a tube with a channel of around 1nm –  the right size to allow small molecules and ions to pass through.
Attached to each of the cyclic peptides are two different types  of polymers, which tend to de-mix and form a shell for the tube with two faces –  hence the name Janus nanotubes.
The faces provide two remarkable properties – in the solid  state, they could be used to make solid state membranes which can act as  molecular ‘sieves’ to separate liquids and gases one molecule at a time. This  property is promising for applications such as water purification, water  desalination and gas storage.
In a solution, they assemble in lipids bilayers, the structure  that forms the membrane of cells, and they organise themselves to form pores  which allow the passage of molecules of precise sizes. In this state they could  be used for the development of new drug systems, by controlling the transport of  small molecules or ions inside cells.
Sebastien Perrier of the University of Warwick said: “There is  an extraordinary amount of activity inside the body to move the right chemicals  in the right amounts both into and out of cells.
“Much of this work is done by channel proteins, for example in  our nervous system where they modulate electrical signals by gating the flow of  ions across the cell membrane.
“As ion channels are a key component of a wide variety of  biological process, for example in cardiac, skeletal and muscle contraction,  T-cell activation and pancreatic beta-cell insulin release, they are a frequent  target in the search for new drugs.
“Our work has created a new type of material – nanotubes – which  can be used to replace these channel processes and can be controlled with a much  higher level of accuracy than natural channel proteins.
“Through a process of molecular engineering – a bit like  molecular Lego – we have assembled the nanotubes from two types of building  blocks – cyclic peptides and polymers.
“Janus nanotubes are a versatile platform for the design of  exciting materials which have a wide range of application, from membranes – for  instance for the purification of water, to therapeutic uses, for the development  of new drug systems.”
Source: University of Warwick
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