Cells continuously sense and respond to the mechanical properties of their environment. They achieve this by forming specialised adhesions through which they exert forces on the extracellular matrix (ECM), a complex, fibrous network that provides structural support and biochemical cues. While it is well established that the mechanical properties of the ECM regulates cellular behaviour, how the nature and subcellular geometry of these adhesion sites regulates force generation and downstream mechanosignalling remains largely unknown.

This PhD project will address this challenge by combining cell biology, biophysical tools, and quantitative analysis to determine how the spatial arrangement of ECM adhesions shapes cellular mechanical responses. The student will investigate how local adhesion geometry affects key readouts such as cytoskeletal organisation, nuclear mechanotransduction, and mechanosensitive transcriptional responses.

Specifically, this project aims to:

Engineer controlled adhesive geometries.
Quantify how adhesion geometry influences cellular force generation, cytoskeletal architecture, and nuclear mechanics.
Determine how extracellular cues are correspond to morphological changes of the nucleus, in turn controlling the localisation of mechanosensitive transcription factors and altering cell fate decisions.

This project will use advanced microfabrication techniques (including photopatterning and rigidity-tuneable hydrogels) to control the localisation of cell-ECM adhesions. To quantify the subsequent cellular responses, we will use a combination of live and fixed fluorescence microscopy in conjunction with quantitative image analysis.

This is an interdisciplinary project that would suit a student with a background in bioengineering, biophysics, or life sciences with an enthusiasm for experimental work and quantitative analysis. Interested candidates are welcome to contact amy.beedle@kcl.ac.uk to discuss the project further.

Lab website: Beedlelab.co.uk

Application Procedure

To be considered for the position candidates must apply via King’s Apply online application system. Details are available at https://www.kcl.ac.uk/study/postgraduate-research/areas/physics-research-mphil-phd.

Please apply for ‘Physics Research MPhil/PhD (full-time) programme' and indicate Dr Amy Beedle as the supervisor and quote the project title in your application and all correspondence.

Please ensure to add '969B' in the Funding section of the application form. Please select option 5 ‘I am applying for a funding award or scholarship administered by King’s College London’ and type the code into the ‘Award Scheme Code or Name’ box. Please copy and paste the code exactly.

The selection process will involve a pre-selection on documents and, if selected, will be followed by an invitation to an interview. If successful at the interview, an offer will be provided in due course.

King’s College London

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Cellular Mechanosensing Regulated by Subcellular Adhesion Geometry