actin filaments

Fungus Toxin Triggers Stem Cells to Become Bone

Imagine you’re riding your bike and an unseen tree root sends you flying over the handlebars. You stick an arm out to break your fall, except the force is too much. The bones in your forearm snap like a twig.

A trip to the hospital means you’ll either get a cast or surgery to realign the broken bones so that they can heal properly. Afterwards, it can take up to six months before the bones fully recover. Now, though, University of North Carolina School of Medicine doctors say there might be something on the horizon to significantly decrease the time it takes for bones to reform after injury. 

In an unexpected find, they watched a toxin called cytochalasin D (CytoD), which is produced by certain molds, cause stem cells to transform into new bone cells. The process can be seen in the gif above, with a stem cell exposed to CytoD beginning the process of turning into a bone cell. After seeing this change occur in cultured cells, Dr. Janet Rubin and colleagues injected it into mouse shinbones, where they witnessed “abundant bone formation” after just one week.

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Hippocampal neuron cultured for 3 weeks and stained for DNA in the nucleus (blue), the microtubule- associated protein MAP2 (green), and actin filaments (red). In mature neurons, MAP2 is present only in cell  bodies and dendrites and absent from axons. Actin filaments are present thoughout the neuron, including axons, but are especially enriched in dendritc spines, which appear as bright red dots along the dendrites.

Two Types of protein filament are involved in contraction

This is the strand which myosin binds to 

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It consists of:

  • Tropomyosin (a rod-shaped protein) molecules coil around F actin, reinforcing it
  • Troponin complex is attached to each tropomyosin molecule
  • Each troponin complex consists of three polypeptides, one binds to actin, one to tropomyosin and one to calcium ions

This is the myosin bundle which consists of many myosin filaments

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  • Each myosin molecule consists of a tail and two protruding heads
  • Each thick filament consists of many myosin molecules whose heads stick out from opposite ends of the filament

THE POWER STROKE / SLIDING FILAMENT MODEL

  1. Myosin head groups attach to the surrounding actin filaments forming a cross-bridge
  2. The head group then bends, causing the thin filament to be pulled along and so overlap more with the thick filament
  3. ADP + Pi are released
  4. The Cross-bridge is then broken as a new ATP molecule attaches to the myosin head
  5. ATP is hydrolysed providing the energy for the myosin head group to moves backwards (re-cocked)
  6. It can now form another cross-bridge and the process is repeated

Telophase

Once chromosomes are pulled to either side, the cell start reversing the steps of prophase and prometaphase: the nuclear envelop reforms around decompacting chromosomes. Near the end of telophase, a thin bridge between the daughter cells, called the midbody contains the remnants of the mitotic spindle. A ring of actin filaments (i.e., the cleavage furrow) pulls like ‘purse strings’ to pinch the cells into two.

Image: Two HeLa cervical cancer cells captured in telophase, as sister chromatids are separated into the two ends of the dumbbell-shaped cell. Green fluorescence is from Aurora B protein kinase fused to eGFP with white and red marking DNA and tubulin. The image was taken using a DeltaVision deconvolution/restoration microscope.

Bone cancer cell (nucleus in light blue)

This image shows an osteosarcoma cell with DNA in blue, energy factories (mitochondria) in yellow and actin filaments, part of the cellular skeleton, in purple. One of the few cancers that originate in the bones, osteosarcoma is extremely rare, with less than a thousand new cases diagnosed each year in the United States.

Image courtesy of Dylan Burnette and Jennifer Lippincott-Schwartz, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Part of the exhibit Life:Magnified by ASCB and NIGMS.

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3D organization of actin filament-based stress fibers at the leading edge of a crawling osteosarcoma cell. This cell was imaged using a super-resolution imaging technique called structured illumination microscopy which yields double the resolution of conventional fluorescent imaging techniques and reveals the 3D structure even in this very flat structure. The Z-positions of actin filaments are color-coded using the rainbow (red, orange, yellow, green, blue, purple) with red representing structures closest to the growth surface and purple at 2.5 microns above the surface. Image : Burnette Lab.

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Q: Where is the best place to see a priceless histological image of a transverse section through a skeletal muscle fiber?

Where indeed….well, the images above show many individual skeletal muscle fibers (cells) cut in cross section. Each fiber is packed full of highly organized arrays of myosin and actin filaments that interact causing the fiber to contract. There is so much actin and myosin crammed into each fiber that their multiple nuclei are forced out to the periphery of the cell.

Individual fibers are surrounded by a connective tissue endomysium then grouped together to form a collection of fibers called a fascicle. Each fascicle is, in turn, surrounded by a connective tissue perimysium. Finally, the many fascicles that make up an entire skeletal muscle are ensheathed within an outer connective tissue epimysium.

So in brief, I guess you coud say that the best place to see a priceless histological image of a transverse section through a skeletal muscle fiber is…

A: In an art mysium

*womp womp*

Thanks everyone for sticking around during my travel chaos.

i-heart-histo

xx