Name: how cells push forward with lamellipodia
Uploaded: 2023-04-30T10:17:09.000Z
Duration: 1 min 31 s
Channel: JoVE

Lamellipodia formation begins with the binding of the growth factors to receptor tyrosine kinase on the cell membrane, thus activating Rac1, a small GTPase, on the cytosolic side.
Next, GTP-bound active Rac1 recruits the WAVE regulatory complex or WRC to the plasma membrane.
WRC activation localizes the IRSp53 protein at the plasma membrane and stimulates the Arp2/3 complex.
The Arp2/3 complex binds pre-existing linear actin filaments and initiates branching, while the localized WRC-IRSp53 complex bends the membrane to form a saddle-shaped curve.
Next, Ena/VASP proteins regulate the capping protein from the plus-end of actin filaments, allowing them to elongate.
As the actin filaments continuously branch and grow, they push the lamellipodium tip forward.
The capping protein limits the length of the branches to form a web of short and rigid actin filaments that broadens the protrusion.
At the same time, cofilin depolymerizes the minus-end of older actin filaments at the back of the web, releasing monomers for reuse at the leading edge.
Thus, actin treadmilling is responsible for the unidirectional extension of the lamellipodia.

mechanism of lamellipodia formation

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for migration.
At the leading edge, the binding of an activated Rac GTPase to the WAVE complex initiates lamellipodia formation. Subsequently, the WAVE complex changes conformation to prime actin nucleators like the Arp2/3 complex for polymerization and branching of filaments. Additionally, members of the formin family localize at the sites of lamellipodia formation, elongating the unbranched filaments. The force generated by continuous actin polymerization pushes the membrane outwards and forms the membrane protrusion. The actin mesh at the leading edge contributes to the formation of focal adhesion points on the ECM, preventing the retraction of lamellipodia.
After lamellipodia formation, the dissociation of filaments begins at the rear end of the dynamic actin meshwork. The actin monomers steadily detach from the minus ends and attach to the plus ends of filaments in the actin network, resulting in treadmilling. This cyclic assembly and disassembly causes&#160; the forward movement of the entire actin filament network even though the position of individual filaments remains stationary to the substratum.
Behind the dynamic lamellipodial meshwork lies a stable network of bundled linear actin filaments called the lamella. This actin network supports the lamellipodium by developing mature and strong adhesion sites, which resist cell compression during migration. Additionally, stable actin filaments of the lamella associate with myosin proteins and use their inherent contractibility to propel the cell forward.

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or ...

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JoVE Core

Cell Biology

Unit 1

Cell Polarization and Migration

KEY TERMS AND CONCEPTS

how cells push forward with lamellipodia

Cells move forward by building lamellipodia, which are thin membrane protrusions at the leading edge. These structures are supported by a mesh of actin filaments that may be linked, branched, or unbranched. Actin works with myosin motor proteins to form the actomyosin complex in the cytoskeleton, and this complex can generate contractile stress. That contractility helps cells sense the stiffness of the extracellular matrix, or ECM, and apply force during migration.

Lamellipodia begin to form when activated Rac GTPase binds to the WAVE complex at the cell front. This binding changes the shape of the WAVE complex and helps activate actin nucleators such as the Arp2/3 complex. Arp2/3 drives actin polymerization and branching, while formin family proteins localize to the same sites and extend unbranched filaments. As actin keeps growing, the force pushes the membrane outward and creates the protrusion.

The growing actin mesh also helps build focal adhesion points on the ECM. These adhesion sites keep the lamellipodium from pulling back. After the protrusion forms, filament breakdown starts at the rear of the dynamic actin network. Actin monomers detach from the minus ends and add to the plus ends, a process called treadmilling. This cycling moves the whole actin network forward even though individual filaments stay in place relative to the substratum.

Behind the active lamellipodial meshwork is the lamella, a more stable network of bundled linear actin filaments. The lamella strengthens the cell by forming mature adhesion sites that resist compression during migration. Its stable actin filaments also associate with myosin proteins. Through their contractile force, they help propel the cell forward.

How Cells Push Forward with Lamellipodia

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Cells move forward by building lamellipodia, which are thin membrane protrusions at the leading edge. These structures are supported by a mesh of actin filaments that may be linked, branched, or unbranched. Actin works with myosin motor proteins to form the actomyosin complex in the cytoskeleton, and this complex can generate contractile stress. That contractility helps cells sense the stiffness of the extracellular matrix, or ECM, and apply force during migration. Lamellipodia begin to form...

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key terms and concepts

Learn how lamellipodia form at the cell edge, how actin treadmilling drives movement, and how the lamella helps cells migrate forward.

How Cells Push Forward with Lamellipodia | JoVE K12

cell biology

JoVE Core Cell Biology illustrates complex cellular processes in easy-to-understand yet comprehensive animated video lessons. This collection focuses on the essential components and functions of cells, including organelles and membranes, cellular transport, and cell energetics. It is complemented by scientist-in-action videos that demonstrate the application of cell biology in real-world research experiments.

How Cells Push Forward with Lamellipodia

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