AMOLF researchers copy self-deforming cell gel
Researchers from the FOM Institute AMOLF and the VU University Amsterdam have created an artificial version of the muscle-like gel that moves and contracts human cells. To their surprise, they discovered that a gel that contains too many 'molecular motors', which enable the gel to contract, becomes overactive and tears itself apart. This finding might explain certain defects that can occur during embryonic growth development. The study is published on 11 August in Nature Physics.
All cells in our body are filled with an active gel, which allows them to move and divide autonomously. The gel, called the cytoskeleton, consists of a network of protein filaments that can contract like a muscle. The researchers have made an artificial version of such a network by combining three components: the protein filaments, 'glue molecules' which hold the gel together, and molecular motors which pull on the fibers during contraction.
It was already known that the cytoskeleton consists of these three components. The molecular motor proteins use stored chemical energy to actively exert internal pulling forces on the protein filaments. The glue molecules, also known as crosslink proteins, connect the filaments into a coherent network.
However, the exact function of these crosslink proteins during cell migration and division was unclear. Researchers from Prof.dr. Gijsje Koenderink's AMOLF group suspected that the crosslinks are needed to transmit the forces generated by the motors across the whole gel. To test this hypothesis, they built a simple artificial version of the gel in the lab: with myosin motor proteins, actin filaments, and fascin crosslinks.
From test tube to computer model
The researchers discovered that the right balance between the three components was essential for the gel to be stable. A gel with too few crosslinks does not form a coherent network, so beneath this critical concentration, the motors cannot contract the gel. Conversely, a concentration of crosslinks that is only just high enough for a network to form will lead to an overactive network that tears itself apart. Only a surprisingly high concentration of glue molecules can prevent the gel from tearing itself into pieces and guarantee that it successfully contracts.
Existing physical models predict that gels will only pull themselves apart at the critical point at which the gel contains just enough crosslinks to create a coherent network of filaments, but in which the tension exerted by the motors can still quickly break these links apart. However, in the lab the researchers discovered that more connected networks, which were far beyond the critical point, also tear themselves apart.
In order to understand why active gels act differently than expected, the researchers from AMOLF worked together with the theoretical physics group of Prof.dr. Fred MacKintosh at VU University Amsterdam. The physicists created a computer model of the active gel and discovered that the motor proteins actively pull the crosslinks apart. This causes the networks to gradually lose their connections until they reach the critical point at which they tear apart.
Self-rupturing networks in biology
These findings can explain a variety of biological phenomena that are observed during the development of organs in embryos. During organ formation, cells that are connected to a sheet on the outer surface of the embryo all contract simultaneously. Recently, biologists found that this sheet in fruit fly embryos spontaneously ruptures if the cells are not connected to each other strongly enough. The new model that was developed by the AMOLF and VU researchers can explain exactly why such defects occur. The researchers hope that these new insights will ultimately help prevent developmental defects.
From smart materials to robots
"The work on biological gels could also lead to new smart materials, which can autonomously change their shape," says Koenderink. "Biological gels could for example be used to repair damaged tissue or organs. Alternatively, synthetic active gels could be used to build robots that can change their shape autonomously. Jose Alvarado, the AMOLF PhD student who is the first author of this study, will test the latter application at the Massachusetts Institute of Technology after the summer, in Prof.dr. Peko Hosoi’s research group."
Both Koenderink and Alvarado were funded by a Vidi grant from the Netherlands Organisation for Scientific Research (NWO).
References
José Alvarado, Michael Sheinman, Abhinav Sharma, Fred MacKintosh, Gijsje Koenderink. Molecular motors robustly drive active gels to a critically connected state. Nature Physics (2013)
Contact
Prof.dr. Gijsje Koenderink, +31 (0)20 754 71 00
Homepage http://www.amolf.nl/research/biological-soft-matter/