Heterogeneity in cell geometric states regulate the selective activation of fibroblasts in engineered 3D tumor microenvironment
Date:
Poster presentation at Mechanobiology after 10 Years: The Promise of Mechanomedicine
Authors: Saradha Venkatachalapathy,Shivashankar G.V.
Abstract
Cancer associated fibroblasts are important regulators of tumor initiation and growth. Recent studies reveal that only subsets of fibroblasts in the stromal microenvironment are activated and the mechanisms that regulate such selective activation is not understood. We propose that the intrinsic mechanical heterogeneity of fibroblasts modulates the nuclear mechano-transduction of signals from the microenvironment, resulting in their selective activation. In this study, we used high resolution images to quantify multiple single cell parameters by which nuclear morphological and organizational features are mapped to the nuclear abundance of transcription factors. We find that the aforementioned parameters are descriptive of the nuclear levels of MKL and p65 in 2D systems. Importantly, using an engineered 3D fibroblast tumor co-culture system, we show that the activation of fibroblasts is dependent on their geometric state. Collectively, our study presents a framework for studying single cell heterogeneity and highlights the importance of geometric state of fibroblasts in the interpretation of environmental signals.