cell biology Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...

, a bleb (or snout) is a bulge of the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

of a cell, characterized by a spherical, "blister-like", bulky morphology. It is characterized by the decoupling of the

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

from the plasma membrane, degrading the internal structure of the cell, allowing the flexibility required for the cell to separate into individual bulges or pockets of the intercellular matrix. Most commonly, blebs are seen in

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

(programmed cell death), but they are also seen in other non-apoptotic functions, including

apocrine Apocrine () is a term used to classify the mode of secretion of exocrine glands. In apocrine secretion, secretory cells accumulate material at their apical ends, often forming blebs or "snouts", and this material then buds off from the cells ...

secretion (cell secretion by disintegration of part of a cell). ''Blebbing'', or ''zeiosis'', is the formation of blebs.

Formation

Initiation and expansion

Bleb growth is driven by intracellular pressure (abnormal growth) generated in the

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

when the actin cortex undergoes actomyosin contractions. The disruption of the membrane-actin cortex interactions are dependent on the activity of myosin-ATPase Bleb initiation is affected by three main factors: high intracellular pressure, decreased amounts of cortex-membrane linker proteins, and deterioration of the actin cortex. The integrity of the connection between the actin cortex and the membrane are dependent on how intact the cortex is and how many proteins link the two structures. When this integrity is compromised, the addition of pressure is able to make the membrane bulge out from the rest of the cell. The presence of only one or two of these factors is often not enough to drive bleb formation. Bleb formation has also been associated with increases in

myosin Myosins () are a Protein family, family of motor proteins (though most often protein complexes) best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are adenosine triphosphate, ATP- ...

contractility and local myosin activity increases. Bleb formation can be initiated in two ways: 1) through local rupture of the cortex or 2) through local detachment of the cortex from the

. This generates a weak spot through which the

flows, leading to the expansion of the bulge of membrane by increasing the surface area through tearing of the membrane from the cortex, during which time, actin levels decrease. The cytoplasmic flow is driven by hydrostatic pressure inside the cell. Before the bleb is able to expand, pressure must build enough to reach a threshold. This threshold is the amount of pressure needed to overcome the resistance of the

to deformation.

Artificial induction

Bleb formation has been artificially induced in multiple lab cell models using different methods. By inserting a micropipette into a cell, the cell can be aspirated rapidly until destruction of cortex-membrane bonds causes blebbing. Breakage of cortex-membrane bonds has also been caused by

laser ablation Laser ablation or photoablation (also called laser blasting) is the process of removing material from a solid (or occasionally liquid) surface by irradiating it with a laser beam. At low laser flux, the material is heated by the absorbed laser ...

and injection of an

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...

depolymerizing drug, which in both cases eventually led to blebbing of the cell membrane. Artificially increased levels of myosin contractility were also shown to induce blebbing in cells. Some viruses, such as the

poxvirus ''Poxviridae'' is a family of double-stranded DNA viruses. Vertebrates and arthropods serve as natural hosts. The family contains 22 genera that are assigned to two subfamilies: ''Chordopoxvirinae'' and ''Entomopoxvirinae''. ''Entomopoxvirinae'' ...

Vaccinia The vaccinia virus (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...

, have been shown to induce blebbing in cells as they bind to surface proteins. Although the exact mechanism is not yet fully understood, this process is crucial to endocytosing the virion and subsequent infection.

Cellular function

Apoptotic function

Blebbing is one of the defined features of

. During apoptosis (programmed cell death), the cell's cytoskeleton breaks up and causes the membrane to bulge outward. These bulges may separate from the cell, taking a portion of

with them, to become known as apoptotic blebs.

Phagocytic cells Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek ...

eventually consume these fragments and the components are recycled. Two types of blebs are recognized in apoptosis. Initially, small surface blebs are formed. During later stages, larger so-called dynamic blebs may appear, which may carry larger organelle fragments such as larger parts of the fragmented apoptotic

cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...

Function in cell migration

Along with

lamellipodia The lamellipodium (: lamellipodia) (from Latin ''lamella'', related to ', "thin sheet", and the Greek radical ''pod-'', "foot") is a cytoskeletal protein actin projection on the leading edge of the cell. It contains a quasi-two-dimensional act ...

, blebs serve an important role in

cell migration Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryogenesis, embryonic development, wound healing and immune system, immune responses all require the orchestrated movemen ...

. Migrating cells are able to polarize the formation of blebs so blebbing only occurs on the leading edge of the cell. A 2D moving cell is able to use adhesive molecules to gain traction in its environment while blebs form at the leading edge. By forming a bleb, the center of mass of the cell shifts forward and an overall movement of cytoplasm is accomplished. Cells have also been known to accomplish 3D bleb-based movement through a process called chimneying. In this process, cells exert pressure on the top and bottom substrates by squeezing themselves, causing a bleb on the leading edge to grow and the cell to have a net movement forward.

Apocrine secretion

Apocrine secretion is the mode of

secretion Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...

exocrine glands Exocrine glands are glands that secrete substances onto an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, prostate and mucous. Exocrine glands are one of ...

wherein secretory cells accumulate material at their apical ends, and this material then buds off from the cells. In many aspects, it can be seen as apoptosis of part of a cell. The secretion process generally initiates with secretory granules accumulating in an ''apical bleb'' (also called "''apical snout''") of the cell, which subsequently disintegrates to release secretory granules into the lumen. File:405 Modes of Secretion by Glands Apocrine.png, Apocrine secretion File:Histology of apocrine cells.png, Histology of apocrine cells, H&E stain.

Miscellaneous functions

Blebbing also has important functions in other cellular processes, including cell locomotion, cell division, and physical or chemical stresses. Blebs have been seen in cultured cells in certain stages of the cell cycle. These blebs are used for cell locomotion in

embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...

. The types of blebs vary greatly, including variations in bleb growth rates, size, contents, and

content. It also plays an important role in all five varieties of

necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who i ...

, a generally detrimental process. However, cell organelles do not spread into necrotic blebs.

Inhibition

In 2004, a chemical known as blebbistatin was shown to inhibit the formation of blebs. This agent was discovered in a screen for small molecule inhibitors of nonmuscle myosin IIA. Blebbistatin allosterically inhibits myosin II by binding near the actin-binding site and ATP-binding site. This interaction stabilizes a form of myosin II that is not bound to actin, thus lowering the affinity of

with

. By interfering with myosin function, blebbistatin alters the contractile forces that impinge on the

-membrane interface and prevents the build up of intracellular pressure needed for blebbing. Blebbistatin has been investigated for its potential medical uses to treat

fibrosis Fibrosis, also known as fibrotic scarring, is the development of fibrous connective tissue in response to an injury. Fibrosis can be a normal connective tissue deposition or excessive tissue deposition caused by a disease. Repeated injuries, ch ...

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

, and

nerve injury Nerve injury is an injury to a nerve. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Herbert Seddon introduced a classification of nerve injuries based on three main types of nerve ...

. However, blebbistatin is known to be

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

photosensitive Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicity. ...

, and

fluorescent Fluorescence is one of two kinds of photoluminescence, the emission of light by a substance that has absorbed light or other electromagnetic radiation. When exposed to ultraviolet radiation, many substances will glow (fluoresce) with color ...

, leading to the development of new derivatives to solve these problems. Some notable derivatives include , , and .

References

External links

{{Wiktionary, bleb
MBInfo - Bleb

MBInfo - Bleb Assembly
Cell anatomy Programmed cell death Cell movement