Lamellipodial actin mechanically links myosin activity with adhesion-site formation.
Cell motility proceeds by cycles of edge protrusion, adhesion, and retraction. Whether these functions are coordinated by biochemical or biomechanical processes is unknown. We find that myosin II pulls the rear of the lamellipodial actin network, causing upward bending, edge retraction, and initiation of new adhesion sites. The network then separates from the edge and condenses over the myosin. Protrusion resumes as lamellipodial actin regenerates from the front and extends rearward until it reaches newly assembled myosin, initiating the next cycle. Upward bending, observed by evanescence and electron microscopy, results in ruffle formation when adhesion strength is low. Correlative fluorescence and electron microscopy shows that the regenerating lamellipodium forms a cohesive, separable layer of actin above the lamellum. Thus, actin polymerization periodically builds a mechanical link, the lamellipodium, connecting myosin motors with the initiation of adhesion sites, suggesting that the major functions driving motility are coordinated by a biomechanical process.
Giannone
Grégory
G
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Dubin-Thaler
Benjamin J
BJ
Rossier
Olivier
O
Cai
Yunfei
Y
Chaga
Oleg
O
Jiang
Guoying
G
Beaver
William
W
Döbereiner
Hans-Günther
HG
Freund
Yoav
Y
Borisy
Gary
G
Sheetz
Michael P
MP
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D005347:Fibroblasts / Q000166:cytology; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010507:Periodicity; D011108:Polymers / Q000378:metabolism; D011554:Pseudopodia / Q000737:chemistry* / Q000648:ultrastructure
D000199:Actins; D011108:Polymers; D024462:Myosin Type II; D009218:Myosins