Inferring cellular contractile forces and work using deep morphology traction microscopy

• Published in: Biophysical journal Vol. 123; no. 18; pp. 3217 - 3230
• Main Authors: Tao, Yuanyuan, Ghagre, Ajinkya, Molter, Clayton W., Clouvel, Anna, Al Rahbani, Jalal, Brown, Claire M., Nowrouzezahrai, Derek, Ehrlicher, Allen J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.09.2024
• ISSN: 0006-3495; 1542-0086; 1542-0086
• DOI: 10.1016/j.bpj.2024.07.020

Traction-force microscopy (TFM) has emerged as a widely used standard methodology to measure cell-generated traction forces and determine their role in regulating cell behavior. While TFM platforms have enabled many discoveries, their implementation remains limited due to complex experimental procedures, specialized substrates, and the ill-posed inverse problem whereby low-magnitude high-frequency noise in the displacement field severely contaminates the resulting traction measurements. Here, we introduce deep morphology traction microscopy (DeepMorphoTM), a deep-learning alternative to conventional TFM approaches. DeepMorphoTM first infers cell-induced substrate displacement solely from a sequence of cell shapes and subsequently computes cellular traction forces, thus avoiding the requirement of a specialized fiduciarily marked deformable substrate or force-free reference image. Rather, this technique drastically simplifies the overall experimental methodology, imaging, and analysis needed to conduct cell-contractility measurements. We demonstrate that DeepMorphoTM quantitatively matches conventional TFM results while offering stability against the biological variability in cell contractility for a given cell shape. Without high-frequency noise in the inferred displacement, DeepMorphoTM also resolves the ill-posedness of traction computation, increasing the consistency and accuracy of traction analysis. We demonstrate the accurate extrapolation across several cell types and substrate materials, suggesting robustness of the methodology. Accordingly, we present DeepMorphoTM as a capable yet simpler alternative to conventional TFM for characterizing cellular contractility in two dimensions.