The contribution of the biomechanics of cells and the extracellular matrix to cancer invasion

Cells and the extracellular matrix (ECM, in particular collagen) are the major elements of tissue. During the course of tumour development, the mechanical properties of both cells and the ECM may vary, contributing to evident changes in the tissue stiffness. However, the nano- to micro-scale dimensions of these species makes them difficult to resolve using current in vivo mapping techniques. Consequently, their role in changes of tissue stiffness is still undefined.

In this project, we aim to develop and use techniques that enable quantitatively measurements of the mechanical properties of tissue elements (i.e. collagen and cells at the nano-and micro-scale) as well as their constructs. This data will then be used in multi-scale analysis of tissue mechanics by us and our collaborators.

To get the experimental data, we will create engineered micropatterns and control the 3D nature of the collagen matrix to modulate cell shape and cell–ECM interactions. Atomic force microscopy (AFM) indentation and traditional micro-indentation will then be use to quantify the stiffness of cells and tissues respectively. The properties of collagen fibres (e.g. orientation, crosslinking, stiffness) prior to and after cell modification will be evaluated with a combination of Raman spectroscopy and AFM. Mathematical models, will be developed by Prof Ray Ogen’s group in Glasgow in parallel with, and informed by, these experimental results. These models will be applied to analyse the relative contributions of the individual components in the tissue and cell/ECM samples. This will enable us to address the important question: What are the relative contributions of cancer cells to alterations of the ECM, tissue stiffness and tumour growth?

Required background:
This PhD project is highly multi-disciplinary, and will run in close collaboration with hospital based clinicians and scientists in local cancer research institutes as well as applied mathematicians. It will allow the student to gain experience in a wide range of desirable skill sets. The project is funded as part of the £2m EPSRC Centre for Multiscale Soft Tissue Mechanics (SofTMech) and the successful candidate will be expected to collaborate with PhD students and scientists involved in the other work packages of the project. Good interpersonal and communication skills are therefore desirable.

Applicants should hold a good 2:1 or 1st class degree in Engineering, Chemistry, Cell Biology, or a related discipline. They should have demonstrated the ability to work effectively in the laboratory. For informal discussion, please contact Dr Huabing Yin with a CV at Email: [Email Address Removed] in the first instance, and for more information on how to apply, see http://www.gla.ac.uk/research/opportunities/howtoapplyforaresearchdegree/.