The goal of this project is to build a new model of muscle contraction called the “winding filament” model. Notwithstanding the success of “sliding filament” model of actin and myosin filaments over 60 years in elucidating the mechanism of muscle contraction, the model still suffers from many problems in predicting muscle’s real mechanical behaviour, especially when the force, length and velocity are changing dynamically. To overcome these limitations, the winding filament model includes “titin”, a giant protein that spans the whole half sarcomere from M-line to Z-disk, as an extra spring-like mechanical component added to the existing sliding filament model. The model hypothesizes that a specific domain of titin (N2A) attaches to and then winds around the actin filament when active cross-bridges are generating torques that rotates the actin filament, which enables the highly tensile domain of titin (PEVK) to store and release the strain energy (Nishikawa et al., 2012). This novel hypothesis can potentially explain many unexplained observations in muscle mechanics. This project will focus on developing a simulation model of skeletal muscle based on the winding filaments model. The model will be tested against empirical observations of muscle behaviour (Yeo et al., 2013) derived from single- fibre in-vitro testing, as well as in-vivo muscle function testing in humans performing lower-limb contractions.
In particular, we will focus on the viscoelasticity during eccentric contraction and residual force enhancement, two long-standing enigmas in muscle mechanics, and see if our new model can provide a viable explanation to the observed data. To assess in-vivo muscle function we will use multi-joint isokinetic / isotonic testing system (Biodex) to measure time course of the knee torque during various leg movements. To assess in-vitro muscle function, we will be collaborating with the Royal Veterinary College in London who have the required expertise and equipment for single-fibre mechanical testing.
Techniques that will be undertaken during the project:
The student will employ the following techniques: - Computational modelling techniques (e.g. using MATLAB) - Testing of human muscle function using a Biodex machine. - In-vitro testing of single-fibre muscle mechanics (The student will receive training from the RVC London).
We are looking for motivated people to participate in the development of experimental protocol, data collection and numerical modelling/analysis. The ideal candidate will have a background in biomechanics and physiology with some experience in human experiment, and will be intimately familiar with running numerical analyses using MATLAB or other programming languages.
Eligibility requirements: An Undergraduate Honours degree with a minimum classification of a 2.1 science BSc or a MSc or equivalent and a life science, clinical or engineering background. English Language qualification for international students.
To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in the School, the funding opportunities available for your subject, and guidance on making your application, you can order a copy of our Doctoral Research Prospectus, at:
http://www.birmingham.ac.uk/drp
