Our paper on the phase-field mixture theory of tumor growth is published in JMPS. The continuum model simulates significant mechano-chemo-biological features of avascular tumor growth in the various microenvironment, i.e., nutrient concentration and mechanical stress.

Faghihi, Feng, Lima, Oden, and Yankeelov (2020). A Coupled Mass Transport and Deformation Theory of Multi-constituent Tumor Growth. Journal of the Mechanics and Physics of Solids, 103936.

https://www.sciencedirect.com/science/article/pii/S0022509620301721

Abstract:

We develop a general class of thermodynamically consistent, continuum models based on mixture theory with phase effects that describe the behavior of a mass of multiple inter- acting constituents. The constituents consist of solid species undergoing large elastic de- formations and incompressible viscous fluids. The fundamental building blocks framing the mixture theories consist of the mass balance law of diffusing species and microscopic (cellular scale) and macroscopic (tissue scale) force balances, as well as energy balance and the entropy production inequality derived from the first and second laws of thermodynamics. A general phase-field framework is developed by closing the system through postulating constitutive equations (i.e., specific forms of free energy and rate of dissipation potentials) to depict the growth of tumors in a microenvironment. A notable feature of this theory is that it contains a unified continuum mechanics framework for addressing the interactions of multiple species evolving in both space and time and involved in biological growth of soft tissues (e.g., tumor cells and nutrients). The formulation also accounts for the regulating roles of the mechanical deformation on the growth of tumors, through a physically and mathematically consistent coupled diffusion and deformation framework. A new algorithm for numerical approximation of the proposed model using mixed finite elements is presented. The results of numerical experiments indicate that the proposed theory captures critical features of avascular tumor growth in the various microenvironment of living tissue, in agreement with the experimental studies in the literature.

Discovering the bio-mechanical signatures of cancer cells in 3D tumouroid models:

We are seeking outstanding candidates for a 4 year PhD studentship fully funded by the UCL Institute of Healthcare Engineering. The student will be jointly supervised by Dr. Emad Moeendarbary based in the Department of Mechanical Engineering and Dr Umber Cheema based at the Division of Surgery and Interventional Sciences.

Studentship Description:

This PhD will entail development of 3D models of solid tumours, which we have termed tumouroids. These tumouroid models are made of up native extra-cellular proteins, and are biomimetic in terms of matrix density, matrix composition, cell spatial positioning and formation of hypoxia gradients. Tumouroids comprise of a dense cancer mass embedded within ‘normal’ tissue stroma. This studentship aims to measure the biomechanical signatures across the tumour-stroma boundary to predict cancer invasiveness. We will use different cell line of cancer with low and high invasive capability and measure stiffness signatures as they develop across the tumour stroma boundary. In addition, we will study the formation of tumour associated collagen signatures and correlate these to mechanical and biological characteristics.

Person Specification:

Essentials:

The candidate is required to have a first class or 2:1 class degree with master’s degree (or equivalent) in biological/ biomedical sciences, mechanical engineering, Physics or a related discipline. The candidate will be expected to be a critical thinker and have the ability to work independently. We also expect the candidate to demonstrate strong verbal and written communication skills, both in plain English and scientific language for communication with academic staff, publication in relevant journals and presentation at conferences.

Desirable:

• Lab experience including; Tissue culture experience; Molecular biology experience, mainly quantitative PCR; 3D biology.
• Experience in any of Atomic Force Microscopy, Advanced Imaging, Microfluidics.
• Flexible, able to work collaboratively
• A strong team player with good interpersonal skills able to build and sustain effective working relationships

Closing Date and Start Date

We will be continuously having an informal discussion with interested candidates until this position is filled. The start date is 23rd September 2019.

Value of Award Stipend

Full tuition fees and a stipend of up to £17,009 per annum for 4 years

Eligibility:

This funding is available for UK and EU passport holders. There is no minimum qualifying residence requirement for applicants from the EU.

Application Process:

Eligible applicants should first contact Dr Emad Moeendarbary ( e.moeendarbary@ucl.ac.uk ). Please enclose a cover letter (including the names and contact details of two referees), one-page research statement and two pages CV. The supervisory team will arrange interviews for short-listed candidates. After interview, the successful candidate will be required to formally apply online via the UCL website. Regrettably, we are only able to contact candidates who are successful at the shortlisting stage. Thank you for your interest in this position.

ABSTRACT: Cell migration is essential for regulating many biological processes in physiological or pathological conditions, including embryonic development and cancer invasion. In vitro and in silico studies suggest that collective cell migration is associated with some biomechanical particularities such as restructuring of extracellular matrix (ECM), stress and force distribution profiles, and reorganization of the cytoskeleton. Therefore, the phenomenon could be understood by an indepth study of cells’ behavior determinants, including but not limited to mechanical cues from the environment and from fellow “travelers”. This review article aims to cover the recent development of experimental and computational methods for studying the biomechanics of collective cell migration during cancer progression and invasion. We also summarized the tested hypotheses regarding the mechanism underlying collective cell migration enabled by these methods. Together, the paper enables a broad overview on the methods and tools currently available to unravel the biophysical mechanisms pertinent to cell collective migration as well as providing perspectives on future development toward eventually deciphering the key mechanisms behind the most lethal feature of cancer.

KEYWORDS: cell mechanics, cancer biophysics, unjamming, collective cell dynamics, cancer invasion, epithelial−mesenchymal transition

https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.8b01428