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

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. 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 highthroughput 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. 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. The platform will enable to perform single cell multi-scale morphometric and molecular live cell data collection (PLAST_DATA) with minimal sample size (<10k cells). Data will be generated based on single molecule-sensitivity marker detection and cellular/subcellular morphodynamic feature recognition via minimal-invasive long-term super-resolution microscopy and parallel morphodynamic imaging of cellular behaviour. Computational integration of PLAST_DATA using preclinical models and patient samples will enable to develop a quantitative classification of tumour cell plasticity and predictive scoring of cancer aggressiveness, metastasis and drug resistance (PLAST_SCORE). 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 technology 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.