2009 Group 10 Project
- 1 The Shape and Cellular structure of a cell
- 2 The Morphology and configuration of cells
- 3 The Cytoskeleton
- 3.1 Actin Filaments
- 3.2 Intermediate Filaments
- 3.3 Microtubules
- 4 Shape Regulation/Function
- 5 Abnormalities
- 6 Current Research
- 7 Glossary
- 8 References
The Shape and Cellular structure of a cell
The Morphology and configuration of cells
The morphology and configuration of a cell depends completely on the precise surface tension and viscosity of the cytoplasm organelle situated within, Countless cellular organelles when separated in a liquid medium have a tendency to develop into a spherical structure, as a result of the principles of surface tension. For instance, in the case of leukocytes (where these specific blood cells are represented as spherical figures), due to the influence of sufficient stimuli released by pseudopodia (amoeboid movement), the cell results in an irregular shape or appearance. Also, the cellular morphology of certain plant and animal cells are exemplified to be polyhedral in shape, determined predominantly by surrounding pressures from adjoining cells and specific proteins. The unique sphere-shaped appearance of the cell is modified by the interactions with the other cells and substances. Cells of diverse categories differ broadly in size and structure. Commonly, prokaryotes, which vary from 1 to 10 microns in width, are smaller than eukaryotes. For instance a single E. coli bacterium calculates to only be approximately two microns in diameter, yet smaller than a individual mitochondrion cell, a eukaryotic structure.
The majority of cells are fairly ordinary. Several animal cellular material are spherical; thus a variety of plant cells are characteristically boxy in appearance. Nevertheless, if observed in more detail, it will appear that a cell's morphology frequently relates directly to its role and function in the organism or structure as well as it behavioral adaptations in it specific environment. For instance, in relation to the outermost distal cells found on the epidermis layer of the skin, the cells are perceived to be compressed and overlap each other like a matrix. Hence the function of the skin acts like a defense mechanism for the human body as it known to be the first line of defense protecting the body's outermost surfaces from foreign pathogens and microbes in the external environment. Neuron cells are even more significant and specialized, resulting in their complex structure and appearance. Neurons have a spherical cell body with a nucleus within it. Neurons also have slender projections, known as dendrites and axons , that broadcast nerve impulses around the body, and thus demonstrating why their morphology is needed to perform specific day to day functions.
In this page, we will be talking about in detail how these different cell morphologies are related to the cytoskeleton. We will go through the different components of the cytoskeleton and their specific properties in great depth to further explain its relation to cell shape. Also, the interaction of the different cytoskeletal component will be discussed and how shape regulation occurs within the cell.
The Histological discovery of the cytoskeleton
The cell shape is established through an elaborate line up of protein fibres. These protein fibres, that are responsible for cell shape, are what we would commonly read as the Cytoskeleton. The cytoskeleton, aside from giving the shell shape, may function in a number of ways. They provide mechanical strength for the cell, enables locomotion, aids in the process of mitosis and meiosis, and also helps in intracellular transport of organelles.
Three different kinds of protein filaments make up the cytoskeleton namely Actin filaments, Intermediate filaments and microtubules.
Actin Filament- Overview
- Actin is spherical protein, approximately 42-kDa established in all eukaryotic cells.
- Recognised as the most extremely-conserved proteins, found in less than 20% of species as diverse specifically in algae and humans organisms.
- One of the three chief mechanisms of the cytoskeleton, in addition to of thin filaments, which are fractions of the contractile apparatus in muscular tissue.
- Actin contributes to many vital cellular functions, including cellular signaling and the organization and preservation of cellular junctions and cell shape.
Actin Filaments are the thinnest of the three proteins, which usually span 8nm. They may also be called microfilaments due to its morphology. These actin filaments are usually found immediately underneath the plasma membrane to provide mechanical strength for the cell. It also may serve the purpose of linking transmembrane proteins to the cytoplasm. These filaments are also responsible for the movement of centrosomes to the opposite poles of the cells during mitosis. Apart from all these functions, they may also facilitate locomotion of the cell. 
Characteristics of Actin filaments
Actin Filament – Function Overview:
Produce a band- like structure underneath the plasma membrane which:
- Offer mechanical strength to the specfic cells
- Links particular proteins (for instance, cell surface receptors) to cytoplasmic proteins for support, its a function charactestic
- Secure the centrosomes during mitosis
- Enables locomotion
- Works together with myosin filaments in skeletal muscular tissue to offer the force for the process of muscular contraction
Actin is a spherical protein that reacts with a catalyst to form actin filaments, otherwise microfilaments which similar to the additional structures of the cellular cytoskeleton construct a three-dimensional complex within eukaryotic cellular material. Actin filaments offer support for the cell, which establish the cell shape and appearance, and facilitate cell activity. Resembling microtubules, numerous actin filaments are unbalanced, except they can also accumulate constant structures in cells, for instance the contractile mechanism of muscle. Actin filaments are linked with an outsized figure of actin- binding proteins that permit the filaments to contribute to a collection of functions within the cells surroundings. In regard to associated proteins variety, Actin filaments are able to produce reasonably stabilized structures for instance the micro-villi on the brush border cells coating the intestine tract.  Video of Actin Filament assembly
Actin Microfilaments arrangements
The spherical actin is recognized as G-actin, despite the fact that the filamentous polymer made of G-actin subunits are identified as F-actin. Microfilaments are known to be the thinnest of the cytoskeleton structures, with a diameter ranging from only 7nm- 8nm. To a large extent similar to the microtubules, actin filaments are acknowledged to be polar, in the company of the plus (+) end lengthening roughly 10 times more rapidly than the minus (-) end segment. The progression of actin polymerization, was established with the involvement of three G-actin monomers into a trimer. ATP-actin subsequently attached the plus segment (+) end, along with the ATP was consequently hydrolyzed, which condenses the binding strong point among adjacent units and commonly undermines the filament. ADP-actin disconnects from the minus segment end and the boost in ADP-actin encourages the substitute of bound ADP for ATP, leading to additional ATP-actin units. This fast reaction is significant for the cells ability to move at a rapid pace.
Cofilin, a specific protein connects to ADP-actin elements and endorses the dissociation from the minus segment end and avoids reattachment. The protein profilin turn around this outcome by stimulating the substitute of bound ADP for ATP. Additionally, ATP-actin units bound to profilin will distances from Cofilin and are then liberated to polymerize. Another significant section in filament construction is the Arp2/3 proteins, which are provided as positions for nucleation, stimulating the configuration of G-actin trimers. The following three process are responsible in regulating cell signaling and movement of cells.
Configuration of Actin filaments
Actin filaments are arranged in two distinct configurations recognized as bundles and networks. Actin-attachment proteins dictate the development of either structure as they cross-link actin filaments. Actin filaments encompass the appearance of a double-stranded twirl. Single filaments are twisted sequences of equal spherical actin molecules, all of which are positioned in the identical bearing along the axis of the sequence; actin filaments are thinner, extra flexible and typically shorter than microtubules segments.
Bundles: Actin filaments and their structures
Actin bundles are categorized into two features of actin bundles: the parallel bundles and contractile bundles. Within the configuration of the parallel bundles, the filaments are distanced 14nm separately by the actin-bundling proteins fimbrin. Parallel bundles are accountable for sustaining cells microvilli which increase the surface area allowing chemicals and particular substance to diffuse across the membrane. In vertebrates, the actin-bundling protein villin is typically origintes in the microvilli of intestinal cells of the digestive tract.
Within contractile bundles, the actin-bundling agent actinin divides every filament component by 40nm. The augment in space permits the motor protein myosin to cooperate with the filament, allowing contraction. During contraction, the myosin particle is typically attached to two individual filaments and both ends concurrently move in the direction of the positive filament end, sliding the actin filaments over each other. This causes the shortening, or contraction, of the actin bundles. This system is accountable for muscle contraction and cytokinesis.
Networks- Actin filaments structures
Actin network branches, among their actin-binding protein, filamin, shape the cells cortex, the surrounding thin layer. This lies under the plasma membrane layer and is accountable for the development of the shape of the cell and it structural appearance.
Dynamic networks of developing actin filaments are significant for many cellular processes, together:
- Cell migration
- Intracellular transport
- Recovery of proteins from the cell surface
The intermediate filaments, as the name implies, are sized between the actin filaments and the microtubules. Intermediate filaments are more rigid structures which are responsible for providing strength and resisting stress, rather than for motility. The nuclear lamins, which stabilise the inner membrane of the nucleus, is a meshwork of intermediate filaments. In neurons, they provide strength and structure for its long processes. They are also responsible for the strength of muscle cells. The intermediate filaments may also contain keratin, which is important for the epithelial cells of the body.
All Intermediate Filaments form a similar structure. It is made up of two polypeptide chains that form a helical structure dimer. The dimer will join with another dimer in an anti-parallel fashion to form a tetramer. The tetramers will then stack together in a head-to-tail manner to form a protofilament, which forms rod-shaped strands. The protofilaments will join together to form an intermediate filament. An intermediate filament is usually comprised of 8 protofilaments. The filaments form a stiff rope-like structure varying in length from 46-53 nm, with an amino-terminal head, a carboxyl-terminal tail and a central rod domain. The end structure of an intermediate filament resembles a rope where smaller filaments would join together.
Most intermediate filaments are homotypic dimers--made of the same kind of protein--though some might show heterodimer properties. Keratins are obligate heterodimers such that they are made up of two different intermediate filament proteins, Type I and II. In contrast, there are other structures that are comprised of one polypeptide, like vimentin. The intermediate filament subunits have rod-shaped domains which are tightly arranged parallel to the filament axis. Unlike other structures, head and tail differentiation of the intermediate filaments are not very clear. The intermediate filaments are said to be apolar structures having no plus and minus ends.
Intermediate filaments are more stable than microfilaments (actin) and microtubules. It is the least dynamic of all the components of the cytoskeleton. Although it is a very rigid structure, it is still capable of alteration through phosphorylation. Phosphorylation regulates the assembly of the intermediate filaments in the cell. This process is most active during mitosis when the nucleus has to be divided and reassembled.
Intermediate Filaments may assemble in 2 different pathways. This process involves the interaction of pre-existing filaments, intermediate filament subunits, and other proteins attaching to the filaments. These 2 pathways are called cotransalational and posttranslational pathways.
The cotranslational pathway involves newly synthesised intermediate filament proteins. The proteins are rapidly incorporated into a soluble region of proteins and are then assembled to become intermediate filaments. This pathway may also involve incorporation of free proteins into multiple sites of the existing intermediate filaments.
The posttranslational pathway is the interaction between existing intermediate filaments. It is a continuous exchange in intermediate filaments along its entire length. This process is unique to intermediate filaments in a way that the microfilaments and microtubules’ protein turnover is limited only to their ends. The posttranslational pathway enables the intermediate filaments to continuously remodel in a gradual approach.
Apart from the two afore mentioned pathways, there are certain domains in the intermediate filaments that play a role in its assembly. Though protein assembly may occur all throughout the entire length of the filament, it is mainly localised in the N-terminal and C-terminal ends. When the disassembly of the filament occurs, it is observed to be transpiring at the C-terminal tail. Likewise, assembly of the filaments occurs in the opposite end, the N-terminal head. Assembly of the intermediate filaments is regulated by protein kinases and the phosphorylation of proteins. This is especially helpful during mitosis when lamins completely disassemble to form 2 nuclei.
Intermediate filaments are rather ubiquitous structures in the cell. They are found prominently in the cytoplasm, and they also comprise the nuclear lamina. Apart from being present inside the cell, they are also positioned in intracellular junctions. They are commonly extending in cell junctions such as desmosomes.
The intermediate filament is an essential component of the nucleus. It maintains the shape of the nucleus and also aids in its division during mitosis. The intermediate filaments form a meshwork called the nuclear lamina. This structure has processes extending into the cytoplasm, which anchors the nucleus in its position. It forms an elaborate structure surrounding the nucleus forming a rigid meshwork. It then spreads out into an intricate network, which extends to the plasma membrane. Nuclear pores, however, interrupt this intermediate filament network. The lamins, which are homologues of the intermediate filaments in the nucleus, differ fromm the rest of the cytoplasmic filaments in that their central rods are longer. They also have specific nuclear signaling which directs them to the nucleus after it has been synthesised in the cytoplasm. The lamins are considerably more dynamic than the rest of the intermediate filaments and disassemble during mitosis.
Also the intermediate filaments extend to join the other components of the cytoskeleton, the actin filaments and microtubules. These components integrate together to form an elaborate meshwork in the cytoplasm. These provide the main structure of the cell.
Aside from being all over the cell, intermediate filaments can also be found in cell junctions. At the cell-cell level of interaction, there are structures called desmosomes. The desmosomes have plakins, a plate-like structure, on either side of the adjacent cells. On these plakins, intermediate filaments are attached. These intermediate filaments span the cell junction to anchor the joining desmosomes together.
Protein Types and Tissue Location
The intermediate filament proteins are classified into 6 different types, according to their location in the cell and the structures they form. Type I to Type IV are proteins that are located in the cytoplasm of the cell. Type V proteins are the primary components of the nuclear lamins. Proteins that do not fall under any of these categories are classified as Type VI proteins. Note that there could be an interaction between these different types of intermediate filament proteins.
Type I and Type II Intermediate Filament Proteins
These groups of proteins are made up of the keratin. They are primarily expressed in skin epithelia, hair and nails. They are highly associated with cell-cell junctions called desmosomes and cell-membrane junctions called hemisdesmosomes. As mentioned above, keratins are obligate heterodimers such that it is made up of both Type I (acidic) and Type II (neutral/basic) proteins. Type I proteins are made of epithelial proteins K9-K20 and hard keratins Ha1-Ha4 for hair and nails. On the other hand, Type II proteins are made up of epithelial proteins K1-K8 and hair keratins Hb1-Hb4. All these proteins integrate to form keratin layers in epithelia. Expressions of these different proteins vary in different tissues (i.e. different proteins would be found in skin epithelia than in cornea epithelia).
Type III Intermediate Filament Proteins
Type III proteins are primarily comprised of vimentin, though it also includes desmin, peripherin and glial fibrillary acidic protein (GFAP). Vimentin, can be found on a number of different cell types. They are expressed in fibroblasts, endothelial cells, the lens and other heamatopoietic cells. Desmin is localised in the muscle cells. It aids the muscle in the structural organisation of the contractile apparatus. It is found in the smooth muscle cell cytoplasm and it also connects the myofibrils of striated muscles . Desmin is found in striated muscles, both in cardiac and skeletal, and smooth muscles. Peripherin is generally localised in the peripheral nervous system. They are often found in the peripheral neurons. Lastly, GFAP is grounded in the central nervous system. They are mostly found in the astrocytes and glial cells. Apart from that, they can also be found in the Schwann cells of the peripheral nervous system, which function for myelination of neurons.
Type IV Intermediate Filament Proteins
This group of proteins is found in the nervous system of the body, both central and peripheral. It is made up of the neurofilament tripet proteins NF-L, NF-M and NF-H. NF-L is the lightest of these 3 proteins and NF-H is the heaviest, hence the nomenclature. NF-L is the core forming proteins while NF-M and NF-H form fibres that extend out as processes. These proteins are essential in the shape formation of the neurons. Any irregularities in neurofilament proteins might result in abnormal axon and/or dendrite development.
Type V Intermediate Filament Proteins
This group of proteins is composed of lamins. They are found in the nuclear lamina, just underneath the nuclear envelope. Lamins are grouped specifically into two: A-type and B-type. The A-type has A and C subclasses which are normally found in differentiating cells. The B-type has B1 and B2 subclasses that are present in the cell in the course of its maturation. They function to keep the shape of the nucleus and also to hold the nucleus within the cytoplasm.
The microtubules, unlike the 2 afore mentioned, are hollow cylinders in structure which are bound by rings called protofilaments. Their dimaters usually span 25 nm and extensively varies in length. These protein structures are made of dimers of alpha tubulin and beta tubulin. This structure are present both in animal and plant cells. This protein is extremely variable that it can grow its ends through polymerisation of dimers and may do otherwise through depolymerisation. Each mictorubule has 2 ends, a plus and a minus end. The plus end achieves more growth and is more active than the minus end. The microtubules mostly functions for the locomotion of the cell.
Tubulin, a protein made of globular molecules, are the basic structural units of microtubules. These tubulin proteins stack together and arrange into strands called protofilaments. Microtubules usually consist of 13 protofilaments arranging side my side to form a cylindrical tube.
Three classes of tubulin protein make up the microtubulues, namely α-tubulin, β-tubulin and γ-tubulin. The α-tubulin and β-tubulin protines alternate along the protofilaments in a polar fashion and stack together to form a protofilament. The plus-end of the microtubule has a beta-tubulin end and the minus-end with the alpha-tubulin. In each tubulin protein, there is a GTP binding site on the plus end surface. This GTP binding site allows for the binding of the next subunit, hence forming long strands, which are the protofilaments. When two tubulin proteins (each consist of alpha and beta subunit) bind together, GTP is locked in the structure and cannot be hydrolysed. These two classes of tubulin proteins are 50% identical in their amino acid sequences. The third class, γ-tubulin, is embedded on the minus end of the microtubules. They are thought to play a role in keeping the stability of the microtubule. It may also act as a template in the formation of microtubules.
Apart from the stacking of tubulin proteins to form the protofilaments, each protofilaments will interact and arranged together to form the hollow structure of the microtubules. This is called the lateral interaction between protofilaments. Each protofilament arranges in a parallel manner. This allows movement of microtubule-associated proteins along the microtubule. In adjacent proteins, the tubulin subunits are aligned in a staggered arrangement. This allows two different lateral arrangements for each pair of protofilaments. The A lattice arrangement is where the subunits of one protofilament interacts with unlike subunits from the adjacent protofilaments (i.e. alpha subunit interacts with beta subunit). The B lattice arrangement happens when like subunits interact allowing a helical symmetry in the structure.
As previously mentioned, microtubules are polar structures due to the arrangement of its alpha and beta subunits. Microtubules have a plus-end and a minus-end. Growth of the structure happens mostly in the plus-end and it is thought that the minus-end is bound to an initiator complex to start assembly. Usually, activity of these ends varies in different stages of the cell. The plus end of the microtubules is very active at the start of assembly. However, the activity starts to slow down and the microtubules shrink. After some time, the microtubule may again be very active and start growing once again.
Stability of the microtubule is dependent on the hydrolysis of GTP (Guanosine Triphosphate). GTP bound to beta-tubulin is hydrolysed as soon as the subunit attaches to an alpha-tubulin. The GTP then becomes a GDP (Guanosine Diphosphate). This leaves an unhydrolysed GTP in the subunit at the end of the plus end. The unhydrolysed GTP provides a site of attachment to the tubulin proteins that will bind in the future. Only the GTP bound to beta-tubulins may be hydrolysed. This hydrolysis results in conformational changes in the prtofilaments leading to instability. The instability of the structure will allow the disassembly or reassembly of the microtubules. Assembly of the tubulin proteins into the microtubules may happen in the plus and minu-end, although it is substantially favored in the plus end. When concentration of tubulin is above critical level, the addition of proteins occurs. However, this is not true for all cases. It is observed that sudden disassembly and shrinkage of the microtubules may occur even when tubulin levels are normal. This process of shrinkage of the microtubule is called catastrophe. When shrinkage arrests and the microtubule start growing again, a process called rescue is happening.
Roles in Cellular Activities
Organelles in the cytoplasm are constantly moving. This movement is aided by the cytoskeletal component of the cell. There are 2 motor proteins that are dependent on microtubules. These are kinesis and Dynein. Both proteins are involved in mitosis and more importantly organelle transport. These two proteins have ATP-binding site, which attach along the microtubules. It is observed that motility of the Endoplasmic Reticulum is majorly dependent on the microtubules. It is noted that the tight meshwork of the endoplasmic reticulum is aligned with the microtubule arrangements. This can be greatly observed in elongating and growing cells. Hence, microtubules play an essential role in the organelle transport within a cell.
Microtubules play an important role in Mitosis, especially in the organization of chromosomes. The nucleation of the microtubules initiates the assembly of the mitotic spindle. The mitotic spindle formed during mitosis is made up of a differently arranged microtubules. These spindles may occur in 3 forms, the spindle apparatus, kinetochores and astral microtubules. The spindle apparatus span from one spindle pole to the other. They serve as a guide for the chromosome to translocate from the metaphase plate to the spindle pole. The kinetochores attach to the centromere of the chromosomes. They allow the sliding of the chrosomes into the spindle apparatus. Lastly, the astral microtubules are structures that anchor the spindle poles in place. They attach the spindle poles to the plasma membrane to avoid its movement while chromosomes are being pulled to the spindle poles.
The shape of a cell serves a vital role in its function. This is seen in structures such as the endothelial cells lining blood vessels. They are simple squamous cells, serving the purpose of allowing a non turbulent flow of blood. If this layer of cells were to differ, consequences would be dramatic. Another example is in neurons, they possess elongated extensions that communicate with adjacent neurons or other cells such as myocytes. This allows distant communication between the two without the use of hormones. This way, the communication is much quicker and a response would be immediate. A structural importance of cells could be see in myocytes, the elongation of the cells allows the group as a whole to exert large amounts of forces. If its structure were to change, the amount of physical force to be produced would diminish.
Shape & Function
Shapes of cells are as diverse as functions they carry out. How do we know which is correct, the shape dictating function or the function dictating shape? Although there are links of function and structure, no detailed research has gone into this field. Genetically, cells are programmed to grow in a certain way. However, a question which arises from a paper by Watson (1991) addresses a topic which pertains to physical forces exerted on cells and whether or not it stimulates certain functions following shapes created. Although the biology of cells are altered by mechanical forces seen in shape changes, for example in myocytes, it may not be a sufficient answer to the question. For cells to respond to a mechanical stimuli in order to change its biological functioning properties, the cell must be able to translate the mechanical stimuli to signals that the cell can comprehend. From this observation, it could be inferred that a certain type of receptor transduces a secondary messenger to respond to cell deformation.
The Role of Extracellular Matrix and Microfilament
At a cellular level, cell shape is determined by a dynamic balance between the contractile and compression forces of microfilaments. These forces have been shown to control cell shapes in fibroblasts and endothelial cells. To understand how mechanical forces affet shapes, we must try to understand that there is a balance carried out within and out side of the cells. The extracellular Matrix is an important determinant of whether the cell will grow, differentiate or go through cell death. The ECM controls cell structure through focal adhesion complex by mutating intracellular cytoskeleton. The intracellular cytoskeleton allocates the positions of most of the cell's metabolic structures that control the overall shape of the cell. Studies with live and membrane permeable cells have demonstrated that shape is a result of mechanical tension generated by microfilaments and the balancing of resistance regions within the extracellular matrix. Molecular studies have shown that ECM controls growth via biochemical and biomechanical signaling. There are studies that have suggested that biochemical and biomechanical are not mutually exclusive but rather works in combination. The receptor complex modifies the cytoskeleton network according to its active state. A signaling molecule such as PKC, may attach to the network activated and so causes a cascade of processes which may or may not change the cell's structure. While simultaneously tension force or stress imposed on the cell may dissociate the signaling molecule from the network and so inhibits a structural change. A combination of both mechanical and biochemical influence allows a level of regulation for the cell's structure.
Cells attain a certain shape suitable for its functional purpose(s). Shape is governed by its ECM and cytoskeleton, which plays an important role in its functional property. Although this is known, there is no in depth knowledge of this relationship. In a study by Sawamoto 1997, they did a study on hepatocytes in cultures to further gain insight into the relationship. Hepatocytes were chosen since their shape and function change with the environment condition that they are in. The study by the group showed that cell proliferation and differentiation can be reciprocally correlated to the cell’s structure. It was demonstrated that hepatocytes with a spherical structure had higher levels of function, but lower potential for growth.The study also demonstrated that cell to cell interaction plays a role on the density of the culture. They showed this by extracting liver "cell surface modulators" and adding them to cell cultures. This resulted in the cells proliferating and differentiation. From this it is also concluded that the cell's function is affected by its morphology.
Proteins Associated with the Cytoskeleton
There are some proteins closely involved in the cytoskeleton function and regulation. A few of these have been researched on by our group such as:
Sickle Cell Anemia
A hereditary disease, also known as deprancytosis, caused by abnormal hemoglobin that changes the shape of red blood cells, Sickle Cell Anaemia, is mostly found to affect people of African or Mediteranean descent with one in 5,000 people having the disease. Hemoglobin is a material that makes up 90% of red blood cells that is used for the transport and intake of oxygen. The heme portion of the hemoglobin contains iron (Fe2+) that attaches to four oxygen molecules and carries them through the blood and releases it in organs. Normal red blood cells contain hemoglobin A and the hereditary disease replaces this hemoglobin A with a mutation called hemoglobin S. This hemoglobin S gives the cell shape a "sickled" shape making them appear as a 'C'. Red blood cells are typically in a concave shape, helping them pass easily through blood vessels. Sickle cells are unable to bend and become more rigid in vessels. The sickle cell makes it difficult for red blood cells to pass through blood vessels causing them to become blocked and built up. Red blood cells are formed by stem cells in bone marrow and are capable of carrying oxygen and carbondioxide back and forth from the lungs to body tissue. Normal red blood cells last about 120 days but sickle cells will only last about ten days, causing a massive decrease in the amount of red blood cells of these patients. With the decrease of oxygen to tissue and the build up of blood cells in vessels, pain, infection and sometimes organ damage can occurs. The lifespan of people with this disorder is shortened to about forty years of age. Patients with sickle cell anemia are at high risk for stroke, acute chest pain, and tissue damage mostly to the spleen, kidneys and liver. There is no cure for this disease but it has been found to benefit areas containing malaria. Malaria is a disease that occurs due to a mosquito bite. After the mosquito bites, it will inject parasites into the blood stream and cause the breakdown on red blood cells. They continue breaking down red blood cells and recreating more parasites. They will eventually live within the red blood cells and can be passed on to other hummans by more mosquitos. Patients with sickle cell anemia, are at an advanatage to not obtaining malaria because the parasites are unable to breakdown their red blood cells easily. Science in not certain why this is true but their are possiblities due to the Hb S found in the cell. The main possility is that the parasites are unable to live with limited oxygen and potassium levels (Bloom, 1995).
Is a rare autosomal recessive hereditary disease causing the premature aging of cells. The mutation occurs on the WRN gene found on chromosome eight. The WRN gene has shown to have abnormalities in the helicase RecQ that corresponds with the DNA replication process. The WRN gene has the role of allowing for the production of the Werner protein. This protein is important in repairing DNA and acts as a helicase enzyme in DNA reproduction. It will separate the double stranded DNA and trim the broken nucleotides off the damaged DNA strands. It's overall main function is to maintain mutated DNA that have been created accidentally. By doing so, it will maintain the function and structure of DNA by helping to replicate and transcribe DNA in cellular division, affecting the lenght of telomeres on chromsomes. If the WRN gene has over 50 abnormalities then Werner's syndrome will infect the patient. The Werner protein will be nonfunctional in the cell nucleus to interact properally with DNA. The protein will decrease in the cell causing disturbed DNA function. Cell's begin to die and the patient begins to physically age. At the early stages, patients show early signs of aging looking over forty years old only in their teenage years. As the disease progresses patients develop diseases often associated with elderly people like cancer, heart problems, high blood pressure,atherosclerosis, cataracts and diabetes. They physically appear to have dwarfism with thin limbs and a larger torso due to abnormal fat deposit. Most patients will die from atherosclerosis or cancer. The life expectancy is only about forty to fifty years of age. The disease occurs in 1 of 400,000 people in the United States but has become more predominant in Japan and China, affecting almost 1 in 40,000 people (Label, 2004).
Duchenne muscular dystrophy
The most severe form of muscular dystrophy causing muscular weakness during childhood is Duchenne Muscular Dystrophy. This is an X-linked disease because the gene is only carried in women but symptoms are shown in males.The duchenne gene is the second largest in humans acounting for 1% of the human genome. The mutation found in the X chromosome causes the abnormality in dystrophin. Dystrophin is a cytoskeleton protein in the sacrolemma that maintains the rigidity of the cell wall in muscle tissue. It has been found in antibody studies to be on the internal side of the plasma membrane and linked to the cytoskeleton by actin. Men having this disease lack the dystrophin protein or contain only 5% in there body. The lack of dystrophin causes the breakdown and decrease of calcium leading to muscle cell death. Muscle fibers die and are replaced with fat tissue. Gower's syndrome is often used to diagnose this disease meaning patients are shown to have weak hip muscles controlling the upper body when trying to stand. Young males will have trouble walking and standing, atrophy will occur and by eight years old they will be in a wheel chair. Due to the replacement of fat in the respiratory and cardiac systems, patients are treated with steroids to help and improve their lifestyle. Because dystrophin can also be found in the brain, about one third of boys will become mentally challenged as their cognitive skills diminsh. The most common way of death will be from cardiac and respiratory failure mostly before the age of twenty. About one in 4,000 males will be born with this hereditary disease (Chamberlain et al, 2006).
Cells within multicellular organisms grow in an environment much softer than the surfaces of the dishes which culture them. The cells mostly attach to the adjacent cells or to the ECM and these structures have an elasticity property between 10 to 10,000 Pa. Ultimately, cell geometry and function is governed by the surrounding environment's stiffness. Previously, studies showed that cells grown on a firmer surface tend to develop flatter and well spreaded out. They also preferentially migrate from a soft surface to a harder and their survival rate differ on the basis of the hardness of the surface on which it is growing on. The current study will study the growth quantitively and qualitively in relations to surface stiffness. Their results indicated that the surface stiffness on which the cells are culture have a profound significance in it's structure and protein expression. Yeung et al demonstrated that endothelial and fibroblast cells grew with a more spreaded structure and actin stress fibers when grown in medium with stiffness of over 2,000 Pa. Neutrophils, however, showed no effect by surface stiffness.
In another research carried out by Bhadriraju et al (2007), they investigated the role of the cytoskeleton tension in the downward cascade of ROCK (Rho-associated kinase). Contractile tension in the cytoskeleton serves an important role in a cell's fate of whether or not to differentiate, proliferate or gene expression. A main controller of cytoskeleton tension is small GTPase RhoA and ROCK, a downstream effector. ROCK phosphorylates myosin binding subunit of myosin phophatase (MYPT1) and myosin light chain (MLC) causes a contractile in the cytoskeleton. By separating the activity of integrin ligation, cell spreading and measuring endogenous RhoA and ROCK they have found that cell shape appears to regulate activity levels of RhoA. Their conclusion aslo includes the fact that they did prove cytoskeleton tension had an effect on RhoA and ROCK activities.
The research article from Jazedje et al (2009) shows that using stem cells from umbilical cord blood, it may be possible to replace the mutatated dystrophin gene in Duchenne muscular dystrophy patients. They show that it may be a possible treatment for these patients to replace the dystrophin. During the project, they were able to compare the CD34+ stem cells of umbilical cord blood and how it differentiated in muscle cells in vitro. These stem cells of DMD patients began to diffuse with muscle cells and after a two week period of incubation, there were areas of positive dystrophin production. Although some tests did not show signs of dystrophin for DMD muscle cells, there are potential for forming the dystrophin muscle cells in vitro. This gives a future hope for patients with DMD to find more stability and possibly a cure for the disease.
- Amino- molecule containing an amine group (NH3)
- Adenosine triphosphate (ATP)- three phosphate groups provided in supplying energy during biochemical processes by undergoing hydrolysis to become adenosine diphosphate (ADP)
- Axon- long, single nerve cell conducting impulses away from the cell body (soma)
- Carboxyl- molecule found in organic acids composed of a carbon bonded to two oxygen and a hydrogen
- Catalyst- enzyme used to enable a chemical reaction that would otherwise be limited
- Cell adhesion- binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules.
- Cell migration- a process in multicellular organism essential for cell growth, differentiation and maintenance. This process involves relocation of specific cells into an area where it will differentiate.
- Collagenase-an enzyme that breaks down peptide bonds of collagen
- Dendrite- process of a neuron cell used to project impulses towards the cell body
- Desmosome- thickening of the plasma membrane on an epithelial cell used to connect two cells
- Epidermis- the outer layer of the skin covering the dermis
- Eukaryote- cell under the taxonomic group containing nuclei and organelles in its' cytoplasm
- Hepatocyte- epithelial cell found in the liver that secretes bile
- Hydrolyze- chemical process involving the splitting of a bond and an addition of two hydrogen atoms
- Keratin- fiber based protein causing the formation of epidermal cells such as hair and nails
- Lamin- a class of interrmediate filaments providing structural function and transcriptional regulation in the cell nucleus.
- Leukocyte- white blood cell that acts as a macrophage, lacks hemoglobin and contains and nucleus
- Matrix metalloproteinase (MMP)- a protease capable of degrading all kinds of extracellular matrix proteins
- Meiosis- the cellular process that passes down one homologous chromosome from each parent cell to a daughter cell
- Microtubule- any small tubule in the eukaryotic cytoskeleton that is composed of the protein tubulin
- Mitochondria cell- membrane enclosed vesicle inside the cytoplasm of a cell and outside the nucleus used for producing and storing energy for cellular processes
- Mitosis- a process that takes place in the nucleus of a dividing cell, involves typically a series of steps consisting of prophase, metaphase, anaphase, and telophase, and results in the formation of two new nuclei each having the same number of chromosomes as the parent nucleus
- Monomer- a chemical compound that can undergo polymerization
- Morphogenesis- differentiating between groups of tissue and organs in chemical or physical process
- Morphology- branch of biology that deals with the form and structure of animals and plants especially with respect to the forms, relations, metamorphoses, and phylogenetic development of organs apart from their functions
- Myosin- globules protein combing with actin to form actomyosin that uses ATP as energy source
- Neuron- cell in the nervous tissue used to transport and accept nervous impulses throughout the body
- Nuclear lamina- a dense network of intermediate filaments inside the nucleus of an eukaryotic cell.
- Nucleus- a cellular organelle of eukaryotes that is essential to cell functions and is composed of nuclear sap and a nucleoprotein-rich network from which chromosomes and nucleoli arise, and is enclosed in a definite membrane
- Pathogen- cell usually bacteria or virus specifically able to cause disease
- Phosphorylation- the process of phosphorylating a chemical compound either by reaction with inorganic phosphate or by transfer of phosphate from another organic phosphate
- Prokaryote- unicellular organism that lack a nucleus and membrane bound organelles
- Protofilament- one of several filaments composing a subunit of a microtubule
- Pseudopodia- temporary projections of the cytoplasm highly associated with amoeboid movement
- RHO- a small family of G proteins that regulate many aspects of intracellular actin dynamics
- Stromelysin- see Matix Metalloproteinases
- Surface tension- the attractive force exerted upon the surface molecules of a liquid by the molecules beneath that tends to draw the surface molecules into the bulk of the liquid and makes the liquid assume the shape having the least surface area
- Trimer- polymer formed from three molecules of a monomer
- Vimentin- a member of the Intermediate filaments family of proteins
- Viscosity-the property of resistance to flow in a fluid or semifluid
Information was taken from MedlinePlus Medical Dictionary
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- Cystoplasmic RNA-binding protein that associates with translating ribosome involved int he organisation of actin filaments
- Actin Filament protein assembly movie
- Actin filaments cross-linking structure diagram
2009 Group Projects
Group 1 Meiosis | Group 2 Cell Death - Apoptosis | Group 3 Cell Division | Group 4 Trk Receptors | Group 5 The Cell Cycle | Group 6 Golgi Apparatus | Group 7 Mitochondria | Group 8 Cell Death - Necrosis | Group 9 Nucleus | Group 10 Cell Shape