Mechanical Properties of Colorectal Cancer Cells Determined by Dynamic Atomic Force Microscopy: A Novel Biomarker.

Abstract

Simple SummaryColorectal cancer (CRC) is presently the third-most abundant and the second-most lethal cancer worldwide. Thus, there is a real and urgent need to investigate the processes behind the appearance, development, and proliferation of CRC cells. Several biochemical pathways have been investigated to understand their role in oncogene activation and tumor-suppressor gene inhibition. Despite the research increase in biochemistry, there is still a need to better understand the biophysical cues that drive the activation of signaling pathways relevant to mechanotransduction and cell transformation. The elucidation of these biological processes may help to hinder oncogenic mechanisms and to find biomarkers that could be used to design more personalized therapeutic strategies.Colorectal cancer (CRC) has been addressed in the framework of molecular, cellular biology, and biochemical traits. A new approach to studying CRC is focused on the relationship between biochemical pathways and biophysical cues, which may contribute to disease understanding and therapy development. Herein, we investigated the mechanical properties of CRC cells, namely, HCT116, HCT15, and SW620, using static and dynamic methodologies by atomic force microscopy (AFM). The static method quantifies Young’s modulus; the dynamic method allows the determination of elasticity, viscosity, and fluidity. AFM results were correlated with confocal laser scanning microscopy and cell migration assay data. The SW620 metastatic cells presented the highest Young’s and storage moduli, with a defined cortical actin ring with distributed F-actin filaments, scarce vinculin expression, abundant total focal adhesions (FAK), and no filopodia formation, which could explain the lessened migratory behavior. In contrast, HCT15 cells presented lower Young’s and storage moduli, high cortical tubulin, less cortical F-actin and less FAK, and more filopodia formation, probably explaining the higher migratory behavior. HCT116 cells presented Young’s and storage moduli values in between the other cell lines, high cortical F-actin expression, intermediate levels of total FAK, and abundant filopodia formation, possibly explaining the highest migratory behavior.