Mechanobiology with FluidFM® 

This application note introduces the basic principle of mechanobiology and notably the use of the FluidFM technology for mechanobiology applications.


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What is mechanobiology?

Mechanobiology - the definition 

The term "mechanobiology" refers to "A field at the interface of biology, physics, and bioengineering, which focuses on how cell/tissue mechanics and physical forces influence cell behavior, cell and tissue morphogenesis, and diseases related to these processes." [1]

Why is mechanobiology so important?

Cells feel and respond to various mechanical signals from their surroundings. The mechanical stiffness of the extracellular matrix strongly determines cell function, stem cell differentiation and tissue homeostasis [2-6]. Oppositely, changes in the matrix stiffness can support the development and spreading of diseases, such as cancer and fibrosis [4]. In addition, cells are often subjected to shear stress due to several physiological processes. In a nutshell, cells are highly sensitive to external forces. Given their central importance in cell function and human health, the literature accumulated has showed that these forces are ubiquitous in vivo. As a result, mechanobiology has emerged as a new and growing field that attracts researchers from various disciplines. The field of mechanobiology comprises a range of field of applications and tools to perform force measurements between various systems and in different environments (air, liquid).

How does mechanobiology work?

In this section, the working principle of mechanobiology applied to single-cell force measurement performed with the FluidFM technology will be explained. An introduction to cell adhesion force is available here. A review of force spectroscopy is accessible here.

Mechanobiology applied - single-cell force spectroscopy with the FluidFM technology

Traditionally, in Single-Cell Force Spectroscopy (SCFS) assays, the object of interest is glued to an AFM cantilever resulting in complex handling and low throughput. The FluidFM systems solve this issue by reversibly immobilizing a cell to a FluidFM probe via suction, and subsequent release with a pressure pulse or brief washing.

This gentle exchange of the cell allows the cantilever to be re-used for several measurements, saves time and costs, and results in a 10 times higher throughput compared to traditional methods. Consequently, both throughput and efficiency of measurements are increased, drastically reducing the time required to obtain statistically relevant data compared to conventional methods. [7] Hence, this technology broadens the possibilities for highly reproducible single-cell adhesion measurements for a broad range of applications. 

FluidFM Mechanobiology - Single cell force spectroscopy

Measure up to 200 cells a day

High throughput obtained with a simple and reversible cell immobilization

Broad force range

Direct and semi-automated force measurement from pN up to µN

Many cell types & colloids

For mammalian cells, microbes, and colloids

Are you interested in an automated single-cell adhesion measurement

Advantages of using FluidFM for mechanobiology

Speed-up your mechanobiology research with a semi-automated single-cell adhesion measurement

 
 

The FluidFM OMNIUM is a semi-automated system for measuring up to 200 single cells a day. Get reproducible, direct force measurements in high quality and with sound statistics.

  

High throughput

  

Direct force measurement

  

Easy-to-use & reproducible

  

Compatible with standard cell-laboratory materials

10x faster measurements compared to standard methods

As objects like cells or colloids can be quickly exchanged through reversible immobilization, measurement throughput is increased more than 10-fold. Up to 200 individual objects can be analyzed in a single day.

FluidFM Mechanobiology - Working principle of single-cell force spectroscopy with FluidFM

Working principle of single cell force spectroscopy with FluidFM.

Simple - no glue needed

The suction method of immobilizing the objects onto the FluidFM cantilever makes it reversible and avoids any glue: Pick. Measure. Release. Repeat.

 
 

Fast & easy. In this video, three micrometer colloids are attracted from suspension with a vacuum, held briefly, and then released again with a pressure pulse.

Switch the probe anytime or reuse to save money

Whether due to degradation, contamination or a required change of probe geometry or chemistry – you can switch the probe at anytime. Just release the object, change the probe, and take up the object again. Our FluidFM Probes typically last for several force spectroscopy measurement days allowing the analysis of several hundred cells.

Many cell types and colloids supported

Cells and colloids come in a wealth of shapes and sizes. FluidFM single-cell force spectroscopy works with adherent or suspension mammalian cells, spheric or rod-shaped microbes, and with colloids, bubbles, and droplets from 0.5 to 100 µm particle size. FluidFM can handle them whether they are hundreds of nm or dozens of µm in diameter. Customers have even analyzed non-colloidal E.coli cells.

 

CellsMicrobesColloids

FluidFM Mechanobiology - Cell

FluidFM Mechanobiology - Microbe

FluidFM Mechanobiology - Colloid

Adherent or suspension cellsSpheric or rod shaped. Algae, bacteria, protozoa, and fungi.
Colloids from 0.5 to 100 µm particle size. Also for bubbles, droplets.
Self-centering – means reproducibility

The position of the object on the FluidFM cantilever is given by the position of the aperture. Thus, every colloidal probe will be centered automatically and at the same position – as long as the same FluidFM Probe is used. This results in highly reproducible positioning. 

FluidFM Mechanobiology - Single cell force spectroscopy

1) cell is selected 2) Cell is detached from surface 3) Resulting force spectroscopy. Image courtesy of Bruker.

10x higher force range

The various stiffnesses and opening diameters of FluidFM Probes enable to measure forces from tens of pN up to µN.

Pick from substrate or attract from solution, or even air

Pick-up cells directly from a substrate or attract them from a solution via liquid influx to the aperture of the FluidFM Probe. This method is also recommended when the long-term adhesion of a microbe to a substrate is too strong to quantify, and hence shorter-term interactions are studied. Researchers have also performed particle and microbe measurements in air.

FluidFM Mechanobiology - Single cell force spectroscopy

S. Cerevisiae, also known as baker’s yeast, are picked-up from medium, measured and then deposited in a line with a FluidFM Micropipette. The cells stay fully viable through this procedure. Image courtesy of P. Dörig, ETH Zurich.

Discuss your experiments with FluidFM experts

Which FluidFM system suits your application?

Do you need a reliable system for your mechanobiology project?

Mechanobiology applications with the FluidFM technology

References

[1] Jansen, Karin A., et al. "A guide to mechanobiology: Where biology and physics meet." Biochimica et Biophysica Acta (BBA)-Molecular Cell Research 1853.11 (2015): 3043-3052.

[2] Engler, Adam J., et al. "Matrix elasticity directs stem cell lineage specification." Cell 126.4 (2006): 677-689.

[3] Orr, A. Wayne, et al. "Mechanisms of mechanotransduction." Developmental cell 10.1 (2006): 11-20.

[4] Lu, Pengfei, Valerie M. Weaver, and Zena Werb. "The extracellular matrix: a dynamic niche in cancer progression." Journal of cell biology 196.4 (2012): 395-406.

[5] Eyckmans, Jeroen, et al. "A hitchhiker's guide to mechanobiology." Developmental cell 21.1 (2011): 35-47.

[6] Wang, J. H-C., and B. P. Thampatty. "An introductory review of cell mechanobiology." Biomechanics and modeling in mechanobiology 5.1 (2006): 1-16.

[7] Dehullu, Jérôme, et al. "Fluidic force microscopy captures amyloid bonds between microbial cells." Trends in microbiology 27.9 (2019): 728-730.