Role of focal adhesions and mechanical stresses in the formation and progression of the lamellipodium-lamellum interface [corrected].
Actin network in the front part of a moving cell is organized into a lamellipodium and a lamellum. A distinct lamellipodium-lamellum interface is associated with focal adhesions and consists of a series of arclike segments linking neighboring focal adhesions in the front row. The interface advances by leaping onto new rows of focal adhesions maturating underneath the lamellipodium. We propose a mechanism of the lamellipodium-lamellum boundary generation, shape formation, and progression based on the elastic stresses generated in the lamellipodial actin gel by its friction against the focal adhesions. The crucial assumption of the model is that stretching stresses trigger actin gel disintegration. We compute the stress distribution throughout the actin gel and show that the gel-disintegrating stresses drive formation of a gel boundary passing through the row of focal adhesions. Our computations recover the lamellipodium-lamellum boundary shapes detected in cells and predict the mode of the boundary transition to the row of the newly maturing focal adhesions in agreement with the experimental observations. The model fully accounts for the current phenomenology of the lamellipodium-lamellum interface formation and advancing, and makes experimentally testable predictions on the dependence of these phenomena on the sizes of the focal adhesions, the character of the focal adhesion distribution on the substrate, and the velocity of the actin retrograde flow with respect to the focal adhesions. The phase diagram resulting from the model provides a background for quantitative classification of different cell types with respect to their ability to form a lamellipodium-lamellum interface. In addition, the model suggests a mechanism of nucleation of the dorsal and arclike actin bundles found in the lamellum.
Shemesh
Tom
T
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
Verkhovsky
Alexander B
AB
Svitkina
Tatyana M
TM
Bershadsky
Alexander D
AD
Kozlov
Michael M
MM
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D003198:Computer Simulation; D003315:Cornea / Q000166:cytology / Q000502:physiology; D004548:Elasticity; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D005399:Fishes; D022001:Focal Adhesions / Q000502:physiology*; D017276:Friction / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D011554:Pseudopodia / Q000502:physiology*; D051381:Rats; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D041701:Swiss 3T3 Cells; D014741:Video Recording; D014981:Xenopus
D000199:Actins