Blebbing is a dynamic cellular process where a cell rapidly forms and retracts rounded, blister-like protrusions on its surface. These temporary structures, known as blebs, are fundamental to cell shape change and are driven by internal forces. Bleb formation involves the plasma membrane pushing outward, resembling a small bubble. While often associated with cell death, blebbing is a general mechanism cells employ for various essential functions, indicating a cell’s ability to respond to its environment.
The Physical Mechanism of Blebbing
Bleb formation is a mechanical process initiated by localized changes to the cell’s underlying scaffolding, the actin-myosin cortex. This dense layer of actin filaments and myosin motor proteins is situated beneath the plasma membrane, providing structural integrity. Blebbing begins when the connection between the plasma membrane and the cortex is locally destabilized or disrupted.
This detachment allows the internal fluid pressure of the cell to push the membrane outward. This outward push is powered by hydrostatic pressure, generated by the active contraction of the rest of the actin-myosin cortex.
The bleb formation process follows a rapid cycle of initiation, expansion, and retraction that typically lasts about one minute. Expansion is rapid, driven by cytoplasm streaming into the protrusion, which is initially devoid of the actin cortex. As the bleb reaches its maximum size, a layer of actin filaments assembles beneath the membrane, forming a temporary cortex.
The recruitment of myosin motor proteins to this cortex initiates the retraction phase. Myosin contracts the newly formed actin network, pulling the bleb membrane back toward the cell body. This cyclical process is regulated by signaling molecules, such as the Rho-associated protein kinase (ROCK), which controls the contractility of the system.
Blebbing in Programmed Cell Death (Apoptosis)
Blebbing is a hallmark of apoptosis, the body’s method of controlled cell suicide. In this context, blebbing signals the execution phase, where the cell is dismantling itself in a non-inflammatory manner to package its contents for disposal.
Apoptosis involves a cascade of molecular events utilizing specialized enzymes called caspases. These caspases break down cellular components and activate the Rho effector protein ROCK I. The resulting over-activation of ROCK I drives an intense, global contraction of the actin-myosin cortex.
This hyper-contractility generates high internal hydrostatic pressure, leading to detachment of the plasma membrane from the cortex. The resulting blebs are larger and more numerous than those seen in non-death processes. These large blebs eventually pinch off, forming membrane-bound sacs called apoptotic bodies.
The formation of apoptotic bodies prevents the release of toxic or inflammatory cellular contents. Cells that die uncontrollably, such as in necrosis, rupture and spill their contents, triggering a significant inflammatory response. Apoptotic blebbing ensures the cell’s internal machinery is securely packaged for immediate recognition and consumption by scavenger cells (phagocytes), clearing the dying cell without causing local inflammation.
Blebbing for Movement and Cell Division
Blebbing serves functions in living cells related to shape change and motility. Bleb-driven motility is a distinct method used by certain immune cells and cancer cells to navigate complex environments. This locomotion is often employed when cells move through confined or three-dimensional spaces, where traditional crawling methods are less effective.
The cell uses blebs as temporary, rapid protrusions that act as anchors to pull the cell forward. A bleb expands quickly, the new actin cortex forms and contracts, and the resulting force pulls the cell body toward the bleb. This mechanism allows for faster, more amoeboid movement compared to slower, actin-polymerization-driven cell crawling.
Blebbing also plays an important role during cytokinesis, the final stage of cell division. As a cell prepares to divide, it must precisely regulate the tension and shape of its surface. Blebbing is often observed at the poles of the dividing cell, away from the central cleavage furrow.
These transient blebs act as mechanisms for localized release of cortical tension, helping to stabilize the cleavage furrow. By locally releasing the pressure, the cell ensures the proper formation and constriction of the contractile ring that separates the two new cells. Unlike apoptotic blebbing, these blebs are quickly and completely retracted.