Mechanobiology of Cell Migration
Scientific Background
The behaviour of cells is significantly affected by the mechanical properties of the
local microenvironment, particularly the stiffness of the substrate. Moreover, there
are fundamental differences in the biomechanics of cell migration on hard and soft
surfaces in terms of focal adhesion turnover, differentiation, stress fibre formation
and cell morphology. Thus, in order to manipulate these cell processes, one needs
to understand how signaling pathways are interconnected with the cellular
machinery and the local mechanical environment. Of particular interest is how cells
behave in an environment relevant to orthopaedic bone grafts and tissue
engineering.
Project
The first aspect of this project will involve creating substrates of varying stiffness
and surface chemistry using a variety of soft polymers and composites made from
these polymer and calcium phosphate (nano)particulate fillers. These materials will
then be characterised using a variety of techniques such as Dynamic Mechanical
Thermal Analysis (DMTA) and Atomic Force Microscopy (AFM). In parallel, the
student will design, fabricate and implement microfluidic devices for controlling
chemotactic cues (both soluble and insoluble spatial gradients). The student will
focus on a well-established cell line models as well as osteoblastic cell lines and
mesenchymal stem cells. Cellular signalling pathways will be manipulated via
molecular biology and pharmacology (siRNA, small molecule, selective inhibitors,
growth factors, cytokines). The effects of these perturbations will be observed via
live-cell imaging; molecular biology techniques including mass spectrometry-based
proteomics will be used to further characterise the resulting signal transduction.
Mathematical modelling will integrate the phenotypic migration response data with
the biochemical signal transduction data, to yield a predictive understanding of how
pharmaceutical intervention can inhibit cell behaviour in varying
microenvironments.
Qualifications: Biomedical or a relevant engineering degree (MS preferred) is
required. Experience in microfluidic design, clean room techniques, and/or animal
cell culture is desired.
Funding: 4 year PhD position (PRTLI5)
Contact details
UCD School of Mechanical and Materials Engineering: http://www.ucd.ie/mme
Systems Biology Ireland: http://www.ucd.ie/sbi/
UCD Bionanosciences Lab: http://bionano.ucd.ie/
To apply, please send cover letter and CV to:
Devrim.kilinc@ucd.ie, by February 1, 2012