Nine out of every ten cancer-related deaths is caused by metastasis, but the molecular mechanisms driving this process are still not fully understood. Several studies have implicated that as a cell’s metastatic potential increases, cell stiffness decreases. Yet while certain genes that affect cell mechanics have been studied, a genome-wide study of networks that modulate cell biophysical properties has not been attempted. The long-term goal of this research is to understand the molecular and mechanical mechanisms driving metastasis. To reach this goal, a new methodology was developed to combine mechanical and gene expression data for the same single cells. Additionally, a novel microfluidics approach for cell sorting based upon biophysical properties was leveraged for the high-throughput discovery of genes linked to cell mechanics and metastasis. These approaches led to deeper understanding of how cellular mechanics are regulated within the context of networks of genes associated with increased metastatic potential. I investigated this intersection by creating and validating a combined single cell mechanics and gene expression methodology, identifying genes related to mechanical changes in cancer cells through GeCKO high-throughput mechanical screen, and validating the phenotypic and mechanotypic importance of genes of
interest.