How do cells decide?
It may come as a surprise that cells in the body possess an inner “compass” that enables them to distinguish between left and right. Researchers at the Mechanobiology Institute (MBI) at NUS have discovered that the compass directing this ability—a capacity vital for the human development process—exists in the form of an actin cytoskeleton, which is an intracellular structure with intrinisic “handedness”. The asymmetric distribution of various tissues and organs is important during embryonic development, as the proper development of a fully functioning human being hinges on this directional decision-making ability of cells.
The work, published in leading journal Nature Cell Biology on 23 March, makes a significant contribution to the understanding that cell behaviour is due to the dynamics of the cell and its microenvironment.
Unlike the rigid human skeletal system that supports the human body, the actin cytoskeleton is constantly remodelling its architecture. Actin is a globular protein that bonds with other actin molecules to form actin filaments, which then organise into more complex structures to form the actin cytoskeleton. This cytoskeleton provides cells with both structural support and a system to generate the forces required for movement.
The MBI research, led by Professor Alexander Bershadsky and Dr Tee Yee Han from the Actin Biomechanics and Cell Dynamics lab at the Institute, uses the “micropatterning” technique to confine single cells onto circular patterns. This allows the team to focus on the study of the actin cytoskeleton dynamics without the influence from the changes in cell shape.
The researchers found that actin organisation displayed a distinct left-right asymmetry reminiscent of a swirling liquid, with actin filaments moving anticlockwise inside the cell. The asymmetry arises when individual actin proteins link to each other in an asymmetric fashion, forming actin filaments with a helical twist resembling the twist in a rope. This intracellular organisation mechanism, where asymmetry of a single protein is translated into the asymmetric behaviour of an entire cell, suggests that asymmetry can originate at the molecular level.
The newly discovered information on whole-cell behaviour provides fresh insight into cellular intelligence, where single cells have the ability to “make decisions”. These findings raise further questions as to how single cell behaviour may impact the consistent left-right asymmetry seen during embryonic development. The possibility that the inherent asymmetry of molecular structures can define cell, tissue or even organism behaviour will have profound implications for future studies into human behaviour and organ development.
