Rapid mechanical phenotyping of breast cancer cells based on stochastic intracellular fluctuations

Predicting the phenotypic impact of genetic variants and treatments is crucial in cancer genetics and precision oncology. Here, we have developed a noise decorrelation method that enables quantitative phase imaging (QPI) with the capability for label-free noninvasive mapping of intracellular dry mass fluctuations within the millisecond-to-second timescale regime, previously inaccessible due to temporal phase noise. Applied to breast cancer cells, this method revealed regions driven by thermal forces and regions of intense activity fueled by ATP hydrolysis. Intriguingly, as malignancy increases, the cells strategically expand these active regions to satisfy increasing energy demands. We propose parameters encapsulating key information about the spatiotemporal distribution of intracellular fluctuations, enabling precise phenotyping. This technique addresses the need for accurate, rapid functional screening methods in cancer medicine.