New Optical Technique Views Cells from Within

Researchers at the University of Notttingham are spearheading the development of a new optical technique to help scientists observe live cells in 4D and understand what triggers them to mutate and spread disease around the human body.

The three-year project will result in a bespoke instrument, combining four cutting-edge optical microscopy technologies in a way that was not possible previously, in a single multifunctional platform.

The tool will image live cells in 4D and plot, track and analyse the cells’ position, movement and function within the proteins and sugars that make up their environment (the extracellular matrix).

This will enable scientists to understand how physical and biochemical cues from cells influence the matrix and vice versa and how these interactions affect disease progression.

"Just as entomologists used to pin dead insects to study their anatomy, until recently life scientists had to 'kill' and fix cell samples to observe them under the microscope. This offered limited insight into cell behaviour," explains project lead, Dr. Amanda Wright, from the Faculty of Engineering, University of Nottingham.

"Today, microscopy has moved on and can now capture 3D images of live cells, but it still isn't advanced enough to explore the crucial interactions that cells have with their surroundings. We need that missing piece of the puzzle to understand the role of cell migration in disease advancement.

"This instrument will revolutionise our understanding of how cells respond to the forces imposed on them by their matrix as they move through it - forces which directly control cell function and behaviour."

The first application of the tool will be to study the spread of breast cancer and how it behaves at different stages of its transformation from benign to malignant and invasive.

"We will be able to view the cellular microworld from a cell's own perspective. It will help us to learn how migrating cancer cells, for example, exploit existing tracts and directional cues inside the matrix," said Dr. Wright.

In addition to cancer, research into degenerative diseases, regenerative medicine and infection pathways could also benefit from this advancement in optical technology.

The more diseases can be replicated and studied in the lab, the better opportunity to apply understanding to inform treatments. This approach is specifically important for developing therapies for diseases where cells respond abnormally to signals from their local matrix, such as cancer.

A second research strand will examine how cells absorb particles and the impact that drug therapies (such as functionalised polymer nanoparticles) have on the matrix. The findings could help to design new medicines and drug delivery systems targeted at the macromolecular level.

Cell/matrix interaction expert Dr. Cathy Merry, from the Faculty of Medicine and Health Science, and Cameron Alexander, Professor of Polymer Therapeutics, in the Faculty of Science are part of the interdisciplinary project team.

The work is also benefiting from the latest imaging and optical trapping research at Heriot Watt University (Drs. Paul Dalgarno and Lynn Paterson) and micro-rheology and data analysis from the University of Glasgow (Dr. Manlio Tassieri), with support from Technology Touching Life, a UK Research and Innovation initiative.