Welcome to the IBMTL

  • Nanostructured, biocompatible scaffold to support 3D cell cultures with controled mechanical properties

    Nanostructured, biocompatible scaffold to support 3D cell cultures with controled mechanical properties [Sonia Contera (Oxford)]

  • MEG data visualization and navigation tool

    MEG data visualization and navigation tool: Synchronization biomarkers of MCI patients [Antonio Gracia (UPM)]

  • High-detailed synapse reconstruction

    High-detailed synapse reconstruction: Electronic microscopy image segmentation by ESPINA software and rendered by GMRV [Marcos Garcia / Angel Rodriguez (URJC/UPM, Cajal Blue Brain)]

  • Numerical model of a neuron under mechanical loading

    Numerical model of a neuron under mechanical loading [Antoine Jerusalem (Oxford)]

  • UPM's 3D virtual reality cave facility

    UPM's 3D virtual reality cave facility: Mini-column reconstruction from microscopy real-time rendered with RTNeuron [Juan Hernando (UPM, Blue Brain Project)]

  • Neurites from SH-SY5Y neurons penetrate through an Isopore membrane

    Neurites from SH-SY5Y neurons penetrate through an Isopore membrane [Hua Ye (Oxford)]

Recent Events:

Second Oxford Brain Mechanics Workshop,
Mathematical Institute, Oxford, Monday 13th and Tuesday 14th January, 2014

Key Publications

(Full list here)

A. Jérusalem, J.A. García, A. Merchán-Pérez and J.M. Peña. A computational model coupling mechanics and electrophysiology in spinal cord injury. Biomechanics and Modeling in Mechanobiology, In press

B. Rashid, M. Destrade, M.D. Gilchrist. Mechanical characterization of brain tissue in tension at dynamic strain rates, Journal of the Mechanical Behavior of Biomedical Materials, Special Issue on Forensic Biomechanics 33 (2014) 43-54.

Babbs and Shi. Subtle paranodal injury slows impulse conduction in myelinated axons. PLoS ONE 8(7): e67767.
doi:10.1371/journal.pone.0067767.

Adekanmbi et al. A novel in-vitro loading system for high frequency loading of cultured tendon fascicles. Medical Engineering & Physics 35:205-10; 2013

Goldstein et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Science Translational Medicine 4:1-16; 2012

Jérusalem and Dao. Continuum modeling of a neuronal cell under blast loading. Acta Biomaterialia 8 (9): 3360-3371; 2012

Castellanos et al. Principles of recovery from traumatic brain injury: Reorganization of functional networks. Neuroimage 55(3):1189-1199; 2011

Raman et al. Mapping nanomechanical properties of live cells using multi-harmonic atomic force microscopy. Nature Nanotechnology 6 (2011) 809-814

Franceschini et al. Brain tissue deforms similarly to filled elastomers and follows consolidation theory. Journal of the Mechanics and Physics of Solids 54:2592-2620; 2006

ABOUT

About the Lab

The International Brain Mechanics and Trauma Lab (IBMTL) is a new international initiative created at the beginning 2013. It involves the collaboration of (as of today) 12 main sites for 21 academics. All 21 academics are currently involved in direct collaborations on projects related to brain mechanics and trauma. This interaction (and the choice of each one of the members) is motivated by the need to gather the following necessary multidisciplinary expertise for the study of the relation between brain cell/tissue mechanics and brain functions/diseases/trauma:

  • Biology: stem cells, tissue engineering, physiopathology
  • Computing: supercomputing, neuroinformatics, image processing, big data analytics
  • Engineering: materials engineering, biomechanics, computational mechanics of materials, mechanobiology
  • Mathematics: mathematical modelling, data mining
  • Medical/Clinical: neurology, neuropathology, neuroscience, magnetoencephalography, veterinary medicine, neurosurgery
  • Neuroscience: translational neuroscience, functional connectivity and brain network architecture, brain plasticity computational modelling
  • Physics: nanoscience, cells/tissues nanomechanics, cell rheology, shockwave/ultrasound physics

This initiative is built around the complementary collaboration of experts of different disciplines around the study of the brain cell and tissue mechanics and its relation with brain functions, diseases or trauma.

News

Events

Second Oxford Brain Mechanics Workshop,
Mathematical Institute, Oxford,
Monday 13th and Tuesday 14th January, 2014

PEOPLE

University of Oxford

Prof. Alain Goriely

Position: Professor of Mathematical Modelling / IBMTL Co-Director
Research interests: Mathematics: Mathematical modelling
Publications: Main list
Home institution webpage

Prof. Antoine Jérusalem

Position: Associate Professor / IBMTL Co-Director
Research interests: Engineering: Computational mechanics of materials
Publications: ResearcherID, Google Scholar
Home institution webpage

Prof. Robin Cleveland

Position: Professor of Engineering Science
Research interests: Engineering: Shock wave/ultrasound physics
Publications: ResearcherID
Home institution webpage

Prof. Sonia Contera

Position: Associate Professor
Research interests: Physics: Nanoscience in medicine, biological physics, scanning probe microscopy
Publications: ResearcherID, Google Scholar
Home institution webpage

Dr. Jayaratnam Jayamohan

Position: Neurosurgeon
Research interests: Clinical: Paediatric neurosurgery, craniofacial surgery
Home institution webpage

Dr. Nick de Pennington

Position: Neurosurgeon
Research interests: Clinical: Neurosurgery
Home institution webpage

Dr. Wayney Squier

Position: Consultant Neuropathologist & Honorary Clinical Lecturer
Research interests: Clinical: Neuropathology
Home institution webpage

Prof. Mark Thompson

Position: Associate Professor
Research interests: Engineering: Biomechanics
Publications: Main list, ResearcherID
Home institution webpage

Prof. Cathy (Hua) Ye

Position: Associate Professor
Research interests: Engineering: Tissue engineering / stem cells
Publications: Main list
Home institution webpage

Boston University

Prof. Lee Goldstein

Position: Associate Professor
Research interests: Medicine/Engineering: Psychiatry, neurology, biomedical engineering
Publications: Main list
Home institution webpage

Dublin City University

Dr Jeremiah Murphy

Position: Lecturer
Research interests: Mathematics: Mathematical modelling
Publications: Main list
Home institution webpage

Graz University of Technology

Prof. Gerhard Holzapfel

Position: Professor
Research interests: Biomechanics: Solid/continuum mechanics
Publications: Main list
Home institution webpage

Massachusetts Institute of Technology

Dr Ming Dao

Position: Principal Research Scientist
Research interests: Materials Science: Cell mechanics
Publications: Main list
Home institution webpage

National University of Ireland, Galway

Prof. Michel Destrade

Position: Professor
Research interests: Mathematics: Mathematical modelling
Publications: Main list, Google Scholar
Home institution webpage

Purdue University

Prof. Riyi Shi

Position: Professor of Neuroscience and Biomedical Engineering
Research interests: Veterinary Medicine/Bioengineering: Translational neuroscience
Publications: Main list
Home institution webpage

Stanford University

Prof. Ellen Kuhl

Position: Associate Professor
Research interests: Engineering: Computational biomechanics
Publications: Main list
Home institution webpage

Technical University of Madrid

Prof. Fernando Maestú

Position: Professor in Cognitive and Computational Neuroscience
Research interests: Cognitive Psychology: MEG/EEG recording for TBI treatment surveillance and prediction
Publications: Google Scholar
Home institution webpage

Prof. José-Maria Peña

Position: Associate Professor in Computer Science
Research interests: Computer Science: Supercomputing, data mining, neuroinformatics, image processing
Publications: Google Scholar
Home institution webpage

University of California, Santa Barbara

Prof. Robert McMeeking

Position: Professor of Mechanical Engineering & Materials
Research interests: Engineering: Solid mechancics
Publications: Main list
Home institution webpage

University of Glasgow

Dr. Peter Stewart

Position: Lecturer
Research interests: Mathematics: Continuum mechanics
Publications: Main list
Home institution webpage

University Pierre & Marie Curie

Fatiha Nothias

Position: Research Director at CNRS
Research interests: Neuroscience: Axon regeneration and growth
Publications: Main list
Home institution webpage

Research Assistants

Antonio LaTorre

Position: Post-doctoral Fellow [JdC, Cajal Blue Brain], UPM, CeSViMa
Project: Image processing and heuristic optimization

Jesus Montes

Position: Post-doctoral Fellow [Cajal Blue Brain], UPM, CeSViMa
Project: Image processing, simulation and data analysis

Lili Zhang

Position: Post-doctoral Researcher, Solid Mechanics Group, University of Oxford
Project: Multiscale cell mechanics modeling

Emily Kwong

Position: Ph.D. Student, Solid Mechanics Group, University of Oxford
Project: Electrophysiological mechanical coupling modelling in neurons

Dongli Li

Position: Ph.D. Student, Healthcare Innovation CDT, University of Oxford
Project: Numerical model of shock wave interactions with cells

PROJECTS

Biomimetic, nanomechanically designed materials for 3-D cell culture and tissue regeneration

Biological systems exploit the physical chemistry of nm-sized biomolecules (proteins, DNA…) to create complex functional, dynamical composite structures with detailed mechanical properties and tailored interfaces with a hierarchical organization (from nm to micron to mm scales), e.g. in the extracellular matrix. These functional structures enable biological function e.g. cell division, morphogenesis and the organization of tissues, and they are altered by disease/trauma. We have concentrated in the fundamental science: we have developed techniques based on the atomic force microscope (AFM) that enable us to study interfaces with sub-nm resolution and to develop techniques based on multifrequency-AFM for mapping mechanical properties of living cells with unprecedented speed and accuracy. Currently we exploit this knowledge to design hybrid bio inspired nanostructures (nanocomposites of biopolymers such as chitosan with nanotubes) for 3-D cell culture and tissue regeneration that enable selectivity and biocompatibility using nanotechnology to design structure, mechanics and interfaces.

People: Dr. S. Contera
Sponsor: Oxford Martin School through Programme on Nanotechnology

Cajal Blue Brain

The Computational Mechanics of Materials group of Dr. Jérusalem, is working on a research new line in collaboration with Prof. Peña of the Computer Science Department of the UPM, within the framework of the Cajal Blue Brain project. The ongoing projects in collaboration with medical and biological communities, and in synergy with de Cajal Blue Brain project´s goals, aim at bringing new simulation tools to the study of brain disease either due to sudden changes in the mechanical properties of the neurons (e.g. TBI) or to slowly evolving dysfunctions (e.g. Alzheimer or Huntington diseases).

People: Prof. J.M. Peña, Antonio LaTorre, Jesus Montes
Sponsor: Spanish Ministry of Science (Special Activities)

Computational Multiscale Neuron Mechanics (COMUNEM)

The last few years have seen a growing interest in computational cell mechanics. This field encompasses different scales ranging from individual monomers, cytoskeleton constituents, up to the full cell. Its focus, fuelled by the development of interdisciplinary collaborative efforts between engineering, computer science and biology, until recently relatively isolated, has allowed for important breakthroughs in bio-medicine/engineering or even neurology. However, the natural "knowledge barrier" between fields often leads to the use of one numerical tool for one bioengineering application with a limited understanding of either the tool or the field of application itself. Few groups, to date, have the knowledge and expertise to properly avoid both pits. Within the computational mechanics realm, new methods aim at bridging scales and modelling techniques; from density functional theory up to continuum modelling on large scale parallel supercomputers. To the best of the knowledge of the author, a thorough and comprehensive research campaign aimed at bridging scales from proteins to the cell level while including its interaction with its surrounding media/stimulus is yet to be done. Among all cells, neurons are at the heart of tremendous medical challenges, and an increased understanding of the intrinsic coupling between mechanical and chemical mechanisms in such cell is of drastic relevance. I thus propose here the development of a neuron model constituted of length-scale dedicated numerical techniques, adequately bridged together. The model will be used for two specific applications: neuron migration/growth and electrophysiological-mechanical coupling in neurons. Upon completion of the project, this multiscale computational framework will be made available to the bioengineering and medical communities to enhance their knowledge on neuron deformation, growth, electro-signaling and thus, on slowly evolving damaging diseases (Alzheimer's disease, epilepsy), as well as more direct damages such as traumatic brain injuries.

People: Dr. A. Jérusalem, Lili Zhang, Emily Kwong
Sponsor: ERC Starting Grant

Engineering Human Neural Networks

The creation of an in-vitro model of the human brain will involve a 'bottom-up' approach by engineering and assembly of 'elements' (synapses), 'units' (neural networks) and 'domains' (structured compartments). The proposed project focuses on the formation of a biological neural network (bNN), capable of learning, initially from NT2.D1 cultures and then human stem cells.

Specifically we will differentiate human stem and NT2.D1 cells into functional neurons, selecting specific scaffolds and optimising culture conditions to direct their growth into 3-D architectures, so facilitating synaptic connection formation. Such screening and optimisation studies will involve multiple parallel perfused microbioreactors. The NT2.D1s will be transfected with channelrhodopsin 2 capability, facilitating axon stimulation through digital light processing.

The bNN's will be formed using guided cell self-assembly and tissue engineering and will involve a blue-light stimulated input layer, (473 nm), followed by an output layer (monitored with Ca2+ imaging). A middle layer will be created using collagen-based constructs. Functional measurement through electrophysiological and optogenetic approaches will monitor action potentials in individual neurons, and synaptic currents will be detected with grid electrodes to observe spiking at the output layer, and 2-photon microscopy will record Ca2+ transients as a measure of net activity.

'Training' of bNNs in pattern recognition by inducing targeted synaptic plasticity will be by repetitive stimulation, so showing ability to distinguish between stimuli. Once self-organized, the bNN's will respond to inputs (supervised learning). Functional bNNs will be monitored in neural plasticity during aging and degeneration. Ultimately, we will create 'functional 'domains', i.e., a large cluster of inter-connected multi-compartment clusters of bNNs, which is effectively artificial human brain tissue.

People: Dr. H. Ye
Sponsor: BBSRC (BB/H008527/1)

Quantitative nanomechanical mapping of live cells with atomic force microscopy

We have recently developed a method based on atomic force microscopy (AFM) (Raman & Trigueros et al Nature Nanotech 2011) that uses the multifrequency response of cantilever as it is scanned over live cell surfaces in physiological conditions to produce a fast quantitative mapping of the properties (stiffness, viscoelasticity) of live cells and tissues that is orders of magnitude faster than previous methods, with a resolution (~ 10nm) sufficient to detail the subcellular and cytoskeletal structures directly involved in mechanotransduction. However this technique is experimentally difficult and data analysis is relatively complex. We are currently developing a method by vibrating the cells at ultrasonic frequencies in the AFM experiment to extend this technique and develop new ones that are more stable and easier to use and analyse in order to map the mechanical properties/rheology of cells in tissues, including subsurface imaging in projects ranging from drug delivery, to tissue regeneration and plant biology.

People: Dr. S. Contera
Sponsors: EPSRC for ECRs grant and Oxford Martin School through Programme on Nanotechnology

Numerical modelling of shockwave interaction with kidney cells

Shock waves have been used medically in lithotripsy (i.e. fragmenting kidney stones) and the treatment for musculoskeletal indications. However, the shock waves can result in undesired damage to healthy tissue. Shock waves also show great potential in cancer therapy by mechanically destroying tumour cells or enhancing sonoporation to effect therapeutic drug delivery. However, the efficacy of these applications and the involved mechanisms are poorly understood. Our numerical work is aimed at understanding the interaction of shock waves and tissue at the cellular level.

In lithotripsy the goal is to minimise soft-tissue injury—an unwanted side-effect from the procedure. For the other therapeutic applications to focus is on understanding the mechanisms of action and optimising the therapeutic effect on the target cells whilst minimising the impact on healthy cells. This work focuses initially on kidney tissue which has both lithotripsy and cancer applications. However, the model can be extended to others organs.

People: Dr. A. Jérusalem, Prof. R. Cleveland, Dongli Li
Sponsor: Healthcare Innovation CDT

RESOURCES

The following resources and facilities are currently available to members of the group:

  • Oxford Supercomputing Centre (OSC)
  • Supercomputing and Visualization Center of Madrid (CeSViMa)
  • Multiphoton microscope
  • Fluorescent microscope
  • Electrospinning apparatus
  • Oxygen plasma system
  • Cell/Tissue culture facilities
  • FTIR
  • HPLC
  • 3D CAVE (5-wall cave automated virtual environment)
  • State-of-the-art scanning probe microscopy
  • SEM, cell and biological specimen preparation lab for in vitro experiments

PUBLICATIONS

CONTACT

Prof. Antoine Jérusalem
Associate Professor
Department of Engineering Science
University of Oxford
Parks Road
Oxford, OX1 3PJ - UK
Tel: +44 (0) 1865 2 83302
Email: antoine.jerusalem AT eng.ox.ac.uk