Abstract

The importance of mechanical force in biology is evident across diverse length scales, ranging from tissue morphogenesis during embryo development to mechanotransduction across single adhesion proteins at the cell surface. Consequently, many force measurement techniques rely on optical microscopy to measure forces being applied by cells on their environment, to visualize specimen deformations due to external forces, or even to directly apply a physical perturbation to the sample via photoablation or optogenetic tools. Recent developments in advanced microscopy offer improved approaches to enhance spatiotemporal resolution, imaging depth, and sample viability. These advances can be coupled with already existing force measurement methods to improve sensitivity, duration and speed, amongst other parameters. However, gaining access to advanced microscopy instrumentation and the expertise necessary to extract meaningful insights from these techniques is an unavoidable hurdle. In this Live Cell Imaging special issue Review, we survey common microscopy-based force measurement techniques and examine how they can be bolstered by emerging microscopy methods. We further explore challenges related to the accompanying data analysis in biomechanical studies and discuss the various resources available to tackle the global issue of technology dissemination, an important avenue for biologists to gain access to pre-commercial instruments that can be leveraged for biomechanical studies.

Highlights

  • Mechanical forces play important roles in many aspects of biology

  • Our Review focuses on the constraints that microscopy places on many mechanobiological techniques, and how emerging advanced microscopy methods can be leveraged to overcome some of these limitations

  • Biomechanical forces underpin a wide array of life processes, ranging from mediating cellular behavior, regulating signaling pathways, sculpting morphogenesis, governing embryonic development, facilitating immune response, to influencing the pathogenesis of many diseases that include cancer, cardiovascular failure, and musculoskeletal disorders

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Summary

Frontiers in Cell and Developmental Biology

Recent developments in advanced microscopy offer improved approaches to enhance spatiotemporal resolution, imaging depth, and sample viability. These advances can be coupled with already existing force measurement methods to improve sensitivity, duration and speed, amongst other parameters. Gaining access to advanced microscopy instrumentation and the expertise necessary to extract meaningful insights from these techniques is an unavoidable hurdle. In this Live Cell Imaging special issue Review, we survey common microscopy-based force measurement techniques and examine how they can be bolstered by emerging microscopy methods.

INTRODUCTION
FORCE MEASUREMENT TECHNIQUES
INTEGRATING ADVANCED LIGHT MICROSCOPY WITH FORCE MEASUREMENTS
Speed and Dimensionality
Imaging Depth
DATA ANALYSIS AND HANDLING
Analysis of Traction Force Microscopy Data
Analysis of FRET Tension Biosensor Data
Findings
DISCUSSION
Full Text
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