Validation of a novel device for real-time, long-term measurement of cellular forces

Introduction

The conventional thinking in cell biology, which often assumes that cells communicate mostly via bio-chemical signalling, has recently been challenged with several examples where mechanical rather than chemical cues play an important role in development, physiology, and disease.

Cellular Forces

Biological cells continually exert forces on their environment, which can vary substantially in magnitude, spatial distribution, and temporal evolution. These forces are key to many processes including:

• Cell growth
• Tissue formation
• Wound healing
• The invasion of cancer cells into healthy tissue

Imaging Challenges

Understanding how cellular forces affect the micro-environment hinges on our ability to image them with sufficient local and temporal resolution. This includes:

1. Continuously over several days with subcellular spatial resolution
2. Adequate field of view to study cell sheets
3. Relevant sensitivity, as typical forces are in the pico to nano Newton range

Despite significant advances made in this area of functional bioimaging over the last years, existing methods still struggle to meet these requirements, thus precluding new commercial opportunities in cell biomechanics.

Project Overview

CELL-FORCE will demonstrate Elastic Resonator Interference Stress Microscopy (ERISM) as a new microscopy method that allows direct, robust, and non-destructive imaging of forces associated with various mechanical cell-substrate interactions, and validate its commercial feasibility.

Advantages of ERISM

The greatly increased sensitivity offered by ERISM over other methods allows for:

• Accurate measurements of vertical forces
• Measurement of cells exerting only weak force

Moreover, with a low light intensity requirement and no need to detach cells after a measurement, using ERISM makes it possible to take long-term measurements of multiple cells without photodamage. This facilitates downstream applications such as immunostaining.

Future Opportunities

This will open up new commercial opportunities in:

• Fundamental research
• Drug development
• (Long-term) diagnostics