Cell blebbing, also known as zeiosis or membrane blebbing, describes a fundamental process where a cell’s outer membrane bulges outward, forming spherical, blister-like protrusions. These dynamic, temporary structures can vary in size, typically growing to about 2 micrometers within 30 seconds before retracting over approximately 120 seconds. Blebs are rounded, fluid-filled sacs extending from the cell surface, a common occurrence across various cellular activities.
How Cells Form Blebs
The formation of blebs is a mechanical process driven by forces within the cell, primarily involving the cytoskeleton, the cell’s internal scaffolding. A component of this scaffolding is the actin cortex, a thin, mesh-like layer of actin filaments located just beneath the cell membrane. This actin cortex contains contractile proteins, notably myosin II, which generate tension.
The process begins with a localized detachment of the plasma membrane from this underlying actin cortex. This detachment can occur through a rupture in the cortex itself or a disruption in the linker proteins connecting the membrane to the cortex. This creates a weak spot in the cell’s surface.
Once a weak spot forms, the cell’s internal pressure, known as intracellular hydrostatic pressure, drives the outward bulging of the membrane. This pressure is generated by the contractile activity of myosin II within the actin cortex. The cytoplasm, the jelly-like substance filling the cell, flows into this newly formed space, causing the bleb to expand. As the bleb expands, new actin cortex can reassemble underneath the bleb membrane, which then helps stop further expansion and initiates retraction.
Why Cells Use Blebbing
Cell blebbing serves multiple functions in healthy cells, contributing to various biological processes. One role is in programmed cell death, or apoptosis. During apoptosis, blebbing is an early sign of cell disassembly, where the cell membrane forms bulges that may eventually separate as “apoptotic bodies” containing cellular components, which are then cleared by other cells.
Blebbing is also involved in cell migration, particularly in amoeboid migration. Cells use blebs to propel themselves forward by forming protrusions at their leading edge, allowing them to navigate through complex environments. This type of movement is distinct from other forms of cell migration, such as those driven by sheet-like protrusions called lamellipodia.
Beyond movement and programmed death, blebbing plays a part in processes like apocrine secretion. In this mode of secretion, cells accumulate secretory material at one end, which then buds off as a bleb, releasing its contents. This mechanism is observed in certain glands, where portions of the cell, along with their contents, are released.
Cell Blebbing and Human Health
Abnormal cell blebbing is recognized for its implications in human health, particularly in disease. A focus area is cancer metastasis, the process by which cancer cells spread from their original site to other parts of the body. Blebbing provides cancer cells with a mechanism to infiltrate surrounding tissues and move through the bloodstream and lymphatic vessels, steps in metastasis.
Cancer cells often exhibit blebbing, a feature less common in normal cells, and this has been linked to more aggressive cancer types, including melanoma and prostate cancer. This phenomenon may enhance cancer cell survival in the bloodstream by providing resilience against shear forces and resisting a type of programmed cell death called anoikis, which is triggered by cell detachment.
Targeting Cell Blebbing
Understanding cell blebbing’s involvement in diseases like cancer has opened avenues for potential therapeutic strategies. Researchers are exploring ways to regulate or inhibit blebbing to interfere with disease progression. Since blebbing is a feature of pro-metastatic tumor cells but generally absent in normal cells, targeting this process could offer a selective approach for cancer therapy with minimal side effects.
One strategy involves inhibiting myosin II, a protein that drives the contractile forces necessary for bleb formation. Experimental compounds like blebbistatin and N-benzyl-p-toluene sulphonamide (BTS) target myosin II activity, thereby inhibiting blebbing. Another approach focuses on blocking signaling pathways downstream of myosin II, such as those involving serine/threonine kinases like Rho-associated kinase (ROCK), which phosphorylate myosin and regulate its activity.