In silico reconstitution of actin-based symmetry breaking and motility.
Eukaryotic cells assemble viscoelastic networks of crosslinked actin filaments to control their shape, mechanical properties, and motility. One important class of actin network is nucleated by the Arp2/3 complex and drives both membrane protrusion at the leading edge of motile cells and intracellular motility of pathogens such as Listeria monocytogenes. These networks can be reconstituted in vitro from purified components to drive the motility of spherical micron-sized beads. An Elastic Gel model has been successful in explaining how these networks break symmetry, but how they produce directed motile force has been less clear. We have combined numerical simulations with in vitro experiments to reconstitute the behavior of these motile actin networks in silico using an Accumulative Particle-Spring (APS) model that builds on the Elastic Gel model, and demonstrates simple intuitive mechanisms for both symmetry breaking and sustained motility. The APS model explains observed transitions between smooth and pulsatile motion as well as subtle variations in network architecture caused by differences in geometry and conditions. Our findings also explain sideways symmetry breaking and motility of elongated beads, and show that elastic recoil, though important for symmetry breaking and pulsatile motion, is not necessary for smooth directional motility. The APS model demonstrates how a small number of viscoelastic network parameters and construction rules suffice to recapture the complex behavior of motile actin networks. The fact that the model not only mirrors our in vitro observations, but also makes novel predictions that we confirm by experiment, suggests that the model captures much of the essence of actin-based motility in this system.
Dayel
Mark J
MJ
Miller Institute for Basic Research in Science, University of California Berkeley, Berkeley, California, USA. markdayel@gmail.com
Akin
Orkun
O
Landeryou
Mark
M
Risca
Viviana
V
Mogilner
Alex
A
Mullins
R Dyche
RD
D008841:Actin Cytoskeleton / Q000378:metabolism; D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002465:Cell Movement; D003198:Computer Simulation; D004548:Elasticity; D006801:Humans; D008089:Listeria monocytogenes / Q000378:metabolism; D008088:Listeriosis / Q000382:microbiology; D008863:Microspheres; D008954:Models, Biological; D008958:Models, Molecular; D009038:Motion
D051376:Actin-Related Protein 2-3 Complex; D000199:Actins