An Atlas of Organisation of Lipids in Extracellular Vesicles To Navigate Their Roles in Cancer Metastasis

Introduction

It is estimated that up to 90% of cancer deaths are caused not by the primary cancer but after it has metastasised, i.e. spread to other organs in the body. It is well known that the locations of metastasised tumours are specific to the location of the primary cancer.

Role of Extracellular Vesicles

Communication and transfer of material between cells is a fundamental process in cell biology, for which nature uses extracellular vesicles (EVs). These nanometre-sized vesicles are excreted by cells and contain signature combinations of:

• Membrane lipids
• Nucleic acids
• Proteins
• Surface markers

EVs excreted by cancer cells play an important role in communication between tumours and distant organs where metastases can take hold.

Overlooked Aspects of EV Research

While more is now understood about the role of EV nucleic acids, proteins, and surface markers in these processes, the role of EV lipid composition, and especially the role of asymmetric lipid distribution across the membrane, remains overlooked.

Research Objectives

I address this fundamental research question by developing an interdisciplinary approach for mapping the asymmetric lipid composition of EVs with varying pro-metastatic nature from a library of cancer cell lines.

1. I will create an atlas of asymmetric lipid compositions of EVs excreted by cancer cell lines.
2. This atlas will include quantitative data on the asymmetric lipid distribution between the inner and outer membrane leaflets (asymmetric lipid distribution).

Methodology

To study the role of EV lipid composition on selective uptake in cells from the original tumour and pre-metastatic environment, I will apply neutron scattering and super-resolution microscopy techniques.

Significance of the Research

Taken together, the atlas of cancer-derived EV asymmetric lipid compositions that I will develop represents a significant advance to the state of the art. It will be a ground-breaking combination of cell biology with engineering-based tools for chemical and biophysical in-depth characterisation of complex, asymmetric membranes.