Three-Dimensional Traction Force Microscopy: A New Tool for Quantifying Cell-Matrix Interactions

TLDR

Cell–matrix interactions are crucial for processes such as wound healing and metastasis, and recent work shows that cells behave differently in three‑dimensional environments compared to two‑dimensional assays, prompting the development of new 3D traction force measurement methods. The study aims to provide a quantitative experimental technique to accurately determine cell traction forces in three dimensions. The authors present a laser‑scanning confocal microscopy–based 3D traction force microscopy method that computes dynamic traction forces during cell migration and locomotion. Applying the method to migrating 3T3 fibroblasts demonstrates its ability to quantify 3D cell‑ECM interactions, offering a new quantitative perspective.

Abstract

The interactions between biochemical processes and mechanical signaling play important roles during various cellular processes such as wound healing, embryogenesis, metastasis, and cell migration. While traditional traction force measurements have provided quantitative information about cell matrix interactions in two dimensions, recent studies have shown significant differences in the behavior and morphology of cells when placed in three-dimensional environments. Hence new quantitative experimental techniques are needed to accurately determine cell traction forces in three dimensions. Recently, two approaches both based on laser scanning confocal microscopy have emerged to address this need. This study highlights the details, implementation and advantages of such a three-dimensional imaging methodology with the capability to compute cellular traction forces dynamically during cell migration and locomotion. An application of this newly developed three-dimensional traction force microscopy (3D TFM) technique to single cell migration studies of 3T3 fibroblasts is presented to show that this methodology offers a new quantitative vantage point to investigate the three-dimensional nature of cell-ECM interactions.