Elastic wrinkling of keratocyte lamellipodia driven by myosin-induced contractile stress

Lou, Sunny S.; Kennard, Andrew S.; Koslover, Elena F.; Gutierrez, Edgar; Groisman, Alexander; Theriot, Julie A.

doi:10.1016/j.bpj.2021.02.022

“…Indeed, fibroblast lamellipodia have previously been seen to buckle due to the force from membrane tension when transitioning from processive to stationary motion on a fibronectin coated coverslip, suggesting there are large compressive forces near the leading edge during certain periods of the protrustion-retraction cycle [79,80]. Buckling has also been seen perpendicular to the leading edge in keratocytes [81].…”

Section: Discussionmentioning

confidence: 99%

Discrete mechanical model of lamellipodial actin network implements molecular clutch mechanism and generates arcs and microspikes

Rutkowski

¹

,

Vavylonis

²

2021

Preprint

0

View full text Add to dashboard Cite

Mechanical forces, actin filament turnover, and adhesion to the extracellular environment regulate lamellipodial protrusions. Computational and mathematical models at the continuum level have been used to investigate the molecular clutch mechanism, calculating the stress profile through the lamellipodium and around focal adhesions. However, the forces and deformations of individual actin filaments have not been considered while interactions between actin networks and actin bundles is not easily accounted with such methods. We develop a filament-level model of a lamellipodial actin network undergoing retrograde flow using 3D Brownian dynamics. Retrograde flow is promoted in simulations by pushing forces from the leading edge (due to actin polymerization), pulling forces (due to molecular motors), and opposed by viscous drag in cytoplasm and focal adhesions. Simulated networks have densities similar to measurements in prior electron micrographs. Connectivity between individual actin segments is maintained by permanent and dynamic crosslinkers. Remodeling of the network occurs via the addition of single actin filaments near the leading edge and via filament bond severing. We investigated how several parameters affect the stress distribution, network deformation and retrograde flow speed. The model captures the decrease in retrograde flow upon increase of focal adhesion strength. The stress profile changes from compression to extension across the leading edge, with regions of filament bending around focal adhesions. The model reproduces the observed reduction in retrograde flow speed upon exposure to cytochalasin D, which halts actin polymerization. Changes in crosslinker concentration and dynamics, as well as in the orientation pattern of newly added filaments demonstrate the model’s ability to generate bundles of filaments perpendicular (actin arcs) or parallel (microspikes) to the protruding direction.

show abstract

“…Indeed, fibroblast lamellipodia have previously been seen to buckle due to the force from membrane tension when transitioning from processive to stationary motion on a fibronectin coated coverslip, suggesting there are large compressive forces near the leading edge during certain periods of the protrusion-retraction cycle [ 85 , 86 ]. Buckling has also been seen perpendicular to the leading edge in keratocytes [ 87 ].…”

Section: Discussionmentioning

confidence: 99%

Discrete mechanical model of lamellipodial actin network implements molecular clutch mechanism and generates arcs and microspikes

Rutkowski

¹

,

Vavylonis

²

2021

View full text Add to dashboard Cite

Mechanical forces, actin filament turnover, and adhesion to the extracellular environment regulate lamellipodial protrusions. Computational and mathematical models at the continuum level have been used to investigate the molecular clutch mechanism, calculating the stress profile through the lamellipodium and around focal adhesions. However, the forces and deformations of individual actin filaments have not been considered while interactions between actin networks and actin bundles is not easily accounted with such methods. We develop a filament-level model of a lamellipodial actin network undergoing retrograde flow using 3D Brownian dynamics. Retrograde flow is promoted in simulations by pushing forces from the leading edge (due to actin polymerization), pulling forces (due to molecular motors), and opposed by viscous drag in cytoplasm and focal adhesions. Simulated networks have densities similar to measurements in prior electron micrographs. Connectivity between individual actin segments is maintained by permanent and dynamic crosslinkers. Remodeling of the network occurs via the addition of single actin filaments near the leading edge and via filament bond severing. We investigated how several parameters affect the stress distribution, network deformation and retrograde flow speed. The model captures the decrease in retrograde flow upon increase of focal adhesion strength. The stress profile changes from compression to extension across the leading edge, with regions of filament bending around focal adhesions. The model reproduces the observed reduction in retrograde flow speed upon exposure to cytochalasin D, which halts actin polymerization. Changes in crosslinker concentration and dynamics, as well as in the orientation pattern of newly added filaments demonstrate the model’s ability to generate bundles of filaments perpendicular (actin arcs) or parallel (microspikes) to the protruding direction.

show abstract

“…Wrinkles penetration depth 𝐿. We use the square of the deviation of the local Gaussian curvature from its average value, Δ𝐾 2 (𝑟, 𝜃) ≡ (𝐾(𝑟, 𝜃) − 〈𝐾〉) 2 , to evaluate the wrinkles penetration depth,…”

Section: Distribution Of the Local Gaussian Curvature As A Function O...mentioning

confidence: 99%

“…For uniaxially stretched thin elastic sheets of thickness b , the minimization of the stretching and bending elastic energies yields λ~ L 0·5 b 0·5 27,28 , where L is the length of the wrinkled domain perpendicular to the wrinkling direction. For discs, this ‘penetration’ length describes how far the undulations propagate radially into the sheet and it can be evaluated from the deviation of the local Gaussian curvature from its average value squared, ΔK 2 ( r, θ ) ≡ ( K ( r, θ ) − ‹ K ›) 2 , which oscillates azimuthally matching the sheet wrinkling deformation. The measured (mean) penetration length L thus corresponds to the distance from the boundary where ΔK 2 ( r ), the azimuthal average of ΔK 2 ( r, θ ), vanishes (Fig.…”

mentioning

confidence: 99%

Artificial contractile actomyosin gels recreate the curved and wrinkling shapes of cells and tissues

Livne

¹

,

Gat

²

,

Armon

³

et al. 2023

Preprint

View full text Add to dashboard Cite

Living systems adopt diversity of shapes. These morphological changes, which range from cell to organismal scales, commonly rely on intrinsic contractile stresses generated by myosin in the cell cytoskeleton, an adaptive active contractile filamentous material, whose molecular constituents, convert chemical energy to produce mechanical work. How these intrinsically active stresses arise in complex 3D shapes and how shape deformation is controlled remains poorly understood. Here, we demonstrate that, initially homogenous not-prepatterned elastic actomyosin networks spontaneously self-organize in a family of 3D shapes through distinct dynamical patterns. Shape selection is encoded in system size to thickness aspect ratio, indicating shaping scalability. The final configurations show surprisingly simple scaling dependence on system dimensions. Altogether, cytoskeletal networks form a class of adaptive active materials, autonomously designing their own shape in response to system geometry, without needing specific pre-programming. This simplicity present huge advantage for developing bio-soft robots with desired target shapes.

show abstract

Elastic wrinkling of keratocyte lamellipodia driven by myosin-induced contractile stress

Cited by 9 publications

References 81 publications

Discrete mechanical model of lamellipodial actin network implements molecular clutch mechanism and generates arcs and microspikes

Discrete mechanical model of lamellipodial actin network implements molecular clutch mechanism and generates arcs and microspikes

Discrete mechanical model of lamellipodial actin network implements molecular clutch mechanism and generates arcs and microspikes

Artificial contractile actomyosin gels recreate the curved and wrinkling shapes of cells and tissues

Contact Info

Product

Resources

About