Cell biomechanics a branch of biomechanics that involves single molecules, molecular interactions, or cells as the system of interest. Cells generate and maintain mechanical forces within their environment as a part of their physiology. Cell biomechanics deals with how mRNA, protein production, and gene expression is affected by said environment and with mechanical properties of isolated molecules or interaction of proteins that make up molecular motors.

It is known that minor alterations in mechanical properties of cells can be an indicator of an infected cell. By studying these mechanical properties, greater insight will be gained in regards to disease. Thus, the goal of understanding cell biomechanics is to combine theoretical, experimental, and computational approaches to construct a realistic description of cell mechanical behaviors to provide new insights on the role of mechanics in disease.

Cell biomechanics

History

In the late seventeenth century, English polymath Robert Hooke and Dutch scientist Antonie van Leeuwenhoek looked into ciliate Vorticella with extreme fluid and cellular motion using a simple optical microscope. In 1702 on Christmas day, van Leeuwenhoek described his observations, “In structure these little animals were fashioned like a bell, and at the round opening they made such a stir, that the particles in the water thereabout were set in motion thereby…which sight I found mightily diverting” in a letter. Prior to this, Brownian motion of particles and organelles within living cells had been discovered as well as theories to measure viscosity. However, there were not enough accessible technical tools to perform these accurate experiments at the time. Thus, mechanical properties within cells were only supported qualitatively by observation.

Cell biomechanics

With these new discoveries, the role of mechanical forces within biology was not always naturally accepted. In 1850, English physician William Benjamin Carpenter wrote “many of the actions taking place in the living body are conformable to the laws of mechanics, has been hastily assumed as justifying the conclusion that all its actions are mechanical." Similarly, in 1917, Scottish mathematical biologist D'Arcy Wentworth Thompson noted “…though they resemble known physical phenomena, their nature is still the subject of much dubiety and discussion, and neither the forms produced nor the forces at work can yet be satisfactorily and simply explained” in his book On Growth and Form.

Cell biomechanics

In the nineteenth century industrialization era, the overall understanding of the cell and tissue mechanics finally developed as it related to the mechanical, structural testing and theory (indentation, beam bending, the Hertz model) of engines, boats, and bridges. At the end of the nineteenth century, the mechanical properties of living cells were able to be experimentally analyzed and examined using techniques provided by large scale engineering mechanics. Since 2008, the nanoscale testing and modeling remains to be fundamentally based on these nineteenth century practices.

Research methods

Various studies have been conducted to establish relationships between the structure, mechanical responses, and function of biological tissues (blood vessels, heart, cardiac muscle, lung). To conduct this research, there have been several developed tools and techniques which are sensitive to detect such small forces. At this time, these techniques are only applicable in a controlled environment (test tube, petri dish). All of these methods ultimately give insight on mechanical properties of cells.

These techniques can generally be split up into two sections: active methods and passive methods. Active methods are methods that apply forces onto cells in some manner to deform the cell. Passive methods are methods that sense mechanical forces and do not apply any external forces to the cell.

Active methods

Atomic force microscopy

Atomic force microscopy is an interaction between a tip attached to a flexible cantilever and the molecule on a cell surface. The sharp tip can be used to probe single molecular events and image live cells. The relative deformation of the cell and the tip can be used to estimate how much force was applied and how stiff the cell is. Since it is a high force measurement technique, large scale deformations and reorganizations can be observed and mapped.

Some drawbacks of this technique include but are not limited to an overestimation of force-versus-indentation curve given no applied force, potential cell damage, variety of tip shapes that determine nature of force-deformation curve.