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

Abstract

Cancer; Cancer systems biology

Càncer; Biologia dels sistemes del càncer

Cáncer; Biología de sistemas del cáncer

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.

This work was partially supported by the Spanish Science and Innovation Ministry through projects RTI2018-099369-B-I00 (related doctoral fellowship [FPI] PRE2019-087448), AES (DTS21/00136)/ISCIII/EU/FEDER, “CELLBIOPHYS” (PID2021-126993OB-I00/MCIN/AEI/10.13039/501100011033/FEDER, UE), “ONCOLIGHT” (PDC2022-133503- I00/MCIN/AEI/10.13039/501100011033/European Union/Next Generation EU/PRTR), and “ONCODEEPLASM” (PLEC2021- 007892/MCIN/AEI/10.13039/501100011033/European Union/Next Generation EU/PRTR) and by Comunidad Autónoma de Madrid (Y2020/BIO- 65194 scCANCER-CM). This work has also been supported by private FERO Foundation and Elena Torres Cancer Association funding. We acknowledge the service from the Micro and Nanofabrication Laboratory and X-SEM laboratory at IMN-CNM funded by the Comunidad Autónoma de Madrid (project S2018/NMT-4291 TEC2SPACE) and by MINECO (project CSIC13-4E-1794 with support from FEDER, FSE).