A multiplexed biomimetic imaging platform for assessing single cell plasticity (Plastomics) and scoring of tumour malignancy

Introduction

Metastasis is the major cause of death in cancer patients due to cancer cell dissemination to distant organs. Cell plasticity is a core characteristic of metastatic cells and confers cellular adaptation capabilities to variable mechano-chemical tissue microenvironments.

Challenges in Measuring Cell Plasticity

However, to date, specific quantitative measures of cancer cell plasticity associated with tumour aggressiveness and therapy resistance have remained difficult to establish. A major limitation is the availability of high-throughput multiplexed assays that can capture phenotypic heterogeneity and morphodynamic plasticity at the single-cell level in standardized 3D culture conditions reflecting in vivo tissue microenvironments.

Project Overview

The PLAST_CELL interdisciplinary consortium will pioneer the development of a microfluidics-based imaging platform to categorize and score cancer cell plasticity within diverse physiologically relevant 3D biomimetic culture conditions.

Key Features of the Platform

The platform will enable the following:

1. Perform single-cell multi-scale morphometric and molecular live cell data collection (PLAST_DATA) with minimal sample size (<10k cells).
2. Generate data based on single molecule-sensitivity marker detection and cellular/subcellular morphodynamic feature recognition via minimal-invasive long-term super-resolution microscopy.
3. Conduct parallel morphodynamic imaging of cellular behaviour.

Data Integration and Impact

Computational integration of PLAST_DATA using preclinical models and patient samples will enable the development of a quantitative classification of tumour cell plasticity and predictive scoring of cancer aggressiveness, metastasis, and drug resistance (PLAST_SCORE).

Implications for Clinical Practice

The ability to assess cell plasticity based on cellular behaviours is beyond current clinical parameters and will strongly impact diagnosis, prognosis, and treatments. The PLAST_CELL platform will be a technological breakthrough to establish new quantitative standards to evaluate cell plasticity and mechanisms of tumour malignancy for a new era of basic research and personalized medicine.