A novel method for sensor-based quantification of single/multi-cellular traction dynamics and remodeling in 3D matrices

Abstract

Cells in vivo generate mechanical forces (traction) on surrounding 3D extra cellular matrix (ECM) and cells. Such traction and biochemical cues may remodel the matrix, e.g. increase stiffness, which in turn influences cell functions and forces. This dynamic reciprocity mediates development and tumorigenesis. Currently, there is no method available to directly quantify single cell traction and matrix remodeling in 3D. Here, we introduce a method to fulfil this long-standing need. We developed a high-resolution microfabricated sensor which hosts a 3D cell-ECM tissue formed by self-assembly. It measures cell forces and tissue-stiffness and can apply mechanical stimulation to the tissue. We measured single and multicellular force dynamics of fibroblasts (3T3), human colon (FET) and lung (A549) cancer cells and cancer associated fibroblasts (CAF05) with 1 nN resolution. Single cells show significant force fluctuations in 3D. FET/CAF co-culture system, mimicking cancer tumor microenvironment, increased tissue stiffness by 3 times within 24 hours.