Abstract

Traction force microscopy (TFM) is a method used to study the forces exerted by cells as they sense and interact with their environment. Cell forces play a role in processes that take place over a wide range of spatiotemporal scales, and so it is desirable that TFM makes use of imaging modalities that can effectively capture the dynamics associated with these processes. To date, confocal microscopy has been the imaging modality of choice to perform TFM in 3D settings, although multiple factors limit its spatiotemporal coverage. We propose traction force optical coherence microscopy (TF-OCM) as a novel technique that may offer enhanced spatial coverage and temporal sampling compared to current methods used for volumetric TFM studies. Reconstructed volumetric OCM data sets were used to compute time-lapse extracellular matrix deformations resulting from cell forces in 3D culture. These matrix deformations revealed clear differences that can be attributed to the dynamic forces exerted by normal versus contractility-inhibited NIH-3T3 fibroblasts embedded within 3D Matrigel matrices. Our results are the first step toward the realization of 3D TF-OCM, and they highlight the potential use of OCM as a platform for advancing cell mechanics research.

Highlights

  • The field of mechanobiology studies the role of material properties and cell forces in physiological and disease processes such as cancer, wound healing, and development

  • To circumvent the limitations imposed by confocal microscopy, while addressing the needs of Traction force microscopy (TFM) studies, we propose the use of optical coherence tomography as a novel platform for 3D TFM

  • We propose traction force optical coherence microscopy (TF-Optical coherence microscopy (OCM)) as a new technique to image cell force – an important biophysical parameter studied in the field of cell mechanics

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Summary

Introduction

The field of mechanobiology studies the role of material properties and cell forces in physiological and disease processes such as cancer, wound healing, and development. Recent work has led to the development of TFM in 3D cell culture, with confocal microscopy taking the lead as the modality of choice to enable imaging of 3D samples and deformations [15, 17, 22,23,24,25,26]. It remains an open area of research how the collective cell behaviors observed in 2D settings will translate within 3D environments

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