Quantitative Analysis of Force Transduction in Human Mammary Epithelial Cell Populations
Dinc, Defne Deniz (2020)
Dinc, Defne Deniz
Åbo Akademi
2020
Julkaisu on tekijänoikeussäännösten alainen. Teosta voi lukea ja tulostaa henkilökohtaista käyttöä varten. Käyttö kaupallisiin tarkoituksiin on kielletty.
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi-fe2020052839510
https://urn.fi/URN:NBN:fi-fe2020052839510
Tiivistelmä
The relationship between cells and their extracellular matrix (ECM) environment is crucial in guiding cell behavior. Cells interpret biochemical and biophysical cues from the ECM through integrin-mediated focal adhesions by exerting forces on the surface they are adhered to. The process of perceiving and responding to the biophysical properties of the ECM is called mechanotransduction. Previous studies describing the role of the ECM niche in the regulation of adult stem cell maintenance and differentiation point out that the biophysical characteristics and the composition of the ECM affect the integrin-mediated mechanotransduction of various types of stem and progenitor cells. However, the mechanobiology of human mammary epithelial cells (HMECs), including the stem and progenitor cells that are likely to contribute to breast tumorigenesis, remains largely unknown. In this study, we aimed to characterize the mechanotransduction of HMECs isolated from primary human breast tissue by quantifying the mechanical forces that the cells exert on a soft (2.6 kPa) hydrogel with the aid of traction force microscopy (TFM). Specifically, we compared the influence of selected ECM ligands, collagen I, fibronectin, or laminin-521, on traction force generation, and identified the basal CD10pos (basal stem cell-enriched) and basal CD10neg HMECs by surface antibody-labeling. Our findings suggest that 1) collagen I-coated hydrogels support the highest and fibronectin-coated hydrogels the lowest traction force generation of primary HMECs, and that 2) the basal stem cell-enriched CD10pos and basal CD10neg HMEC populations display similar mechanoresponses on ligand-coated soft hydrogels. This initial exploration of HMEC mechanobiology suggests differential responses to ECM ligands and will serve as a starting point for the discovery of new niche regulatory mechanisms in the human mammary gland. More importantly, the findings of this study data may turn out to be relevant also for the mechanical regulation of cancer stem cells in breast tumors.