Overview

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.

Blebbing Through the Matrix

In multicellular organisms,  migrating cells navigate through a complex three-dimensional path, squeezing their way between cells and through the extracellular matrix (ECM). The actin-driven membrane protrusions, such as filopodia  and lamellipodia, aid in crawling across surfaces or between cells. In contrast, blebs allow the cells to navigate through narrow gaps between the components of the ECM. The initiation and expansion of blebs push the flexible plasma membrane through these small gaps while subsequent  bleb retraction helps move the cell through this three-dimensional matrix.

Blebbing and Apoptosis

Apoptosis or programmed cell death is a sequential cascade of events that aid the death of a cell without damaging surrounding cells. Blebbing is a characteristic feature of this process. An apoptotic cell initiates multiple blebs on its surface, which pinch off to form tiny apoptotic blebs containing bits of cytoplasm and proteins from the primary cell. Other cells such as neutrophils and macrophages phagocytose these apoptotic blebs, and help recycle the cellular components. Apoptotic cells also produce larger blebs containing fragments of disrupted organelles such as mitochondria and nucleus. 

Procedure

The cell is internally lined with an actomyosin network that forms the cortex, and is linked to the cell membrane via linker proteins such as ezrin.

In response to appropriate signals, the cortical actin network destabilizes and ruptures, leading to localized detachment of the membrane from the cortex.

The internal hydrostatic pressure causes the detached membrane to swell outwards and rapidly fill with the cytoplasm, forming a rounded protrusion called a bleb.

Inside the bleb, a cytoskeletal regulator, Rnd3, prevents RhoA activation and inhibits the reassembly of the actin cortex, allowing further expansion of the bleb.

As the bleb expands, the Rnd3 concentration decreases, resulting in RhoA activation.

Activated RhoA promotes reassembly of actin and ezrin, thus re-establishing the cortex in the bleb.

Finally, myosin-II associates with and contracts the actin bundles, generating the force to retract the bleb and push the cell forward through the extracellular matrix.