Extended Data Fig. 5: Simulations of protruding and ruffling lamellipodia show increased drag in viscous medium.
From: Membrane ruffling is a mechanosensor of extracellular fluid viscosity
a) Ruffles in 1% MC experience drag two orders of magnitude greater than ruffles in regular medium. Ruffling was modeled as a periodic behavior with a 20-second period starting with the cell membrane at the leading edge detaching from the substrate to which it was adhered. b,c) Maximal and average drag forces on a protruding lamellipodia in DMEM and in 1% MC were estimated using finite element analysis. d) Force decomposition shows that the force generated by actin to drive protrusion, FProtrusion, and the retrograde forces of contractility and tension that ultimately lead to ruffling, FRetrograde, are oriented almost exclusively in the xy-plane; therefore, FRuffle, the z-oriented component of FRetrograde directly responsible for initiating ruffles, is extremely small. e) In the lamellipodium, the force required to cause buckling increases proportionally with the coefficient of viscous drag. In highly viscous medium, cells are incapable of generating the greatly increased forces required to cause buckling to the same extent as in regular medium; instead, lamellipodial buckling is reduced.
