Enhancing Robustness, Precision and Speed of Traction Force Microscopy with Machine Learning

Abstract

Traction patterns of adherent cells provide important information on their interaction with the environment, cell migration or tissue patterns and morphogenesis. Traction force microscopy is a method aimed at revealing these traction patterns for adherent cells on engineered substrates with known constitutive elastic properties from deformation information obtained from substrate images. Conventionally, the substrate deformation information is processed by numerical algorithms of varying complexity to give the corresponding traction field via solution of an ill-posed inverse elastic problem. We explore the capabilities of a deep convolutional neural network as a computationally more efficient and robust approach to solve this inversion problem. We develop a general purpose training process based on collections of circular force patches as synthetic training data, which can be subjected to different noise levels for additional robustness. The performance and the robustness of our approach against noise is systematically characterized for synthetic data, artificial cell models and real cell images, which are subjected to different noise levels. A comparison to state-of-the-art Bayesian Fourier transform traction cytometry reveals the precision, robustness, and speed improvements achieved by our approach, leading to an acceleration of traction force microscopy methods in practical applications. O_TEXTBOXSIGNIFICANCETraction force microscopy is an important biophysical technique to gain quantitative information about forces exerted by adherent cells. It relies on solving an inverse problem to obtain cellular traction forces from image-based displacement information. We present a deep convolutional neural network as a computationally more efficient and robust approach to solve this ill-posed inversion problem. We characterize the performance and the robustness of our approach against noise systematically for synthetic data, artificial cell models and real cell images, which are subjected to different noise levels and compare performance and robustness to state-of-the-art Bayesian Fourier transform traction cytometry. We demonstrate that machine learning can enhance robustness, precision and speed in traction force microscopy. C_TEXTBOX