Microstructure of passive and active F-actin solutions and networks
visualized by electron microscopy (A–C) and fluorescence microscopy (A–C
Insets, E, and F). (A) Passive solutions are isotropic, homogeneous, and unbundled.
(B) Active solutions ([myosin]/[actin] 0.02 and 5 mMATP) are still homogeneous
(Inset), but the myosin locally aligns and bundles the actin filaments. (C)
Active networks ([FLNa]/[actin] 0.005, [myosin]/[actin] 0.02, 5 mM ATP) are
macroscopically homogeneous, but small contractile foci are present (Inset); the
actin filaments extending out from these foci are bundled and aligned, but they
merge into a more isotropic network between the foci. (D) Proposed mechanism
of active stiffening: myosin filaments (blue) contract actin filaments (gray) toward
one another, thereby pulling against the FLNa cross-links (red) and generating
an internal stress. (E and F) Passive networks cross-linked by rigor myosin (0
mM ATP) show bundles and clumps, both in the presence (E) and absence (F) of
FLNa. For all panels, [actin]23.8M, and the average filament length is 15m.
F actin is fluorescently labeled by Alexa488-phalloidin. (Scale bars: InsetsA–C and
F, 10 m; A–C, 200 nm; E, 20 m).
A quivering blob of muscle proteins in a Harvard lab could lead to controllable biomaterials to replace damaged body tissue.
Under a microscope, the “active gel” looks like a throbbing tangle of fibres immersed in jelly. Created by David Weitz and his colleagues at Harvard University, it is made from a molecular net of the muscle protein actin held into shape by another protein, filamin. Each actin strand has around 300 molecules of another muscle protein, myosin, attached.
The gel stiffens when exposed to ATP, the chemical that cells use to store and release energy. It becomes 1000 times firmer, a change in elasticity of the same order as Jell-O setting, says Weitz.
The myosin molecules flex like miniature biceps, bunching up the actin strands and causing the network to “tense up”.
The blob is similar to the adaptable but tough protein skeleton that as well as holding cells in shape also allows them to shape-shift as required, she says.
Weitz thinks his active gel design could be used to give a new twist to tissue engineering, which usually involves using a static scaffold to guide the growth of replacement tissues from stem cells.
Scaffolds with tunable elasticity could allow more complex structures to be grown, says Weitz. For example, a floppy, untensed blob could be moved into position and then set in place with a pulse of ATP.
We describe an active polymer network in which processive molecular motors control network elasticity. This system consists of actin filaments cross-linked by filamin A (FLNa) and contracted by bipolar filaments of muscle myosin II. The myosin motors stiffen the network by more than two orders of magnitude by pulling on actin filaments anchored in the network by FLNa cross-links, thereby generating internal stress. The stiffening response closely mimics the effects of external stress applied by mechanical shear. Both internal and external stresses can drive the network into a highly nonlinear, stiffened regime. The active stress reaches values that are equivalent to an external stress of 14 Pa, consistent with a 1-pN force per myosin head. This active network mimics many mechanical properties of cells and suggests that adherent cells exert mechanical control by operating in a nonlinear regime where cell stiffness is sensitive to changes in motor activity. This design principle may be applicable to engineering novel biologically inspired, active materials that adjust their own stiffness by internal catalytic control.
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