Curtis Lambert
4/22/22
Word Count: 1020
Scientific Literacy Essay Final
Cells play an irreplaceable role in the biological systems of living organisms. In complex organisms they are the components of all organs and living tissue; and as one would expect, carry out vital processes necessary for the proper functioning of the organism. Although their function is irreplaceable, sometimes the cells themselves need to be replaced. In addition to this, sometimes cells need to be “deleted” as a routine part of biological process or because they are no longer required for any significant biological process. When a cell needs to properly destroy itself, it must undergo a process known as apoptosis.
Apoptosis, or programmed cell death, is a natural aspect of the cells that make up the body of many living organisms. It is utilized to remove cells that are no longer needed, like some of the cells that exist during the embryotic stage of human development. It also aids in the removal of cells that could be cancerous or cells that have been infected with a virus. In the article “Apoptosis: A Review of Programmed Cell Death” Elmore (2017) discusses how apoptosis can be triggered through a number of different ways, and not all cells respond the same way to identical stimuli. It can be triggered by the cell through internal pathways or through external stimuli to the cell. After getting the signal to undergo apoptosis, the first thing the cell does is shrink. Because of the shrinkage, the organelles within begin to get pushed closed to one another. With all of this, nuclear chromatin fragments begin to condense and become compact. It is at this stage that the dying cell begins budding, this describes the process of the plasma membrane blebbing, which then fragment into cell pieces called apoptotic bodies. These apoptotic bodies are comprised of cytoplasm with condensed organelles. Parenchymal cells, neoplastic cells or macrophages will ensure that the apoptotic bodies get phagocytosed. With the apoptotic bodies removed, the cell is effectively destroyed.
During the process of apoptosis, the cell undergoes radical morphological alterations. A key component in the morphological structure of the cell is the cytoskeleton. The cytoskeleton maintains the structural integrity of the cell and has mechanical properties that aid the cell in other processes. An article titled (Microtubules and Filaments, 2014, nature.com) explains how the cytoskeleton consists of protein filaments. The protein tubulin makes up the microtubules; and the protein actin makes up the actin filaments. Microtubules are larger than actin filaments. Without these proteins the cytoskeleton would suffer significantly decreased function. In the research article titled “Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis” by (Caruso et al., 2019) the researchers focus their attention on apoptosis. They further investigate the role of the cytoskeleton during the morphological changes in the cell that occur during apoptosis. They are specifically interested in gaining insights on the development of apoptopodia, which is a membrane protrusion that resembles tiny balls strung along a thin piece of wire. The researchers in this article conducted multiple studies to discern if the cytoskeleton is involved with the formation of apoptopodia in any way. They do this by targeting actin and tubulin and observing if the membrane protrusion associated with apoptopodia formation will still occur in the dying cell.
The researchers first set up an experiment in which Jurkat T cells were induced into apoptosis using ultraviolet radiation. The Jurkat T cells were then exposed to an inhibitor to induce apoptotic cell disassembly. This was done in a 3D culture model, and similar to results yielded using a cell suspension model, the human Jurkat T cells formed apoptopodia. THP-1 cells were also observed to generate beaded apoptopodia in cell suspension and in 3D cultures after being irradiated. These findings are significant because combined with other confirming data, they suggest that apoptotic membrane protrusion can occur in cells grown in suspension as well as cells grown in 3D culture environments.
A variety of research methods were utilized involving the examination of apoptopodia under different conditions. F actin was monitored using a cell permeable probe called SiR-actin. A staining method was used on the plasma membrane to better identify apoptopodia. A similar permeable probe method was utilized to observe microtubule distribution during the apoptotic cell disassembly process. The probe utilized in observing microtubule distribution is called SiR-tubulin. The role of vimentin was examined by targeting it using “a doxycycline (dox)-inducible CRISPR/ Cas9-based approach” (Caruso et al., 2019, p. 868) with the Jurkat T cells. Apoptotic body formation was examined while inhibiting actin and tubulin polymerization. Microtubule spikes were investigated because they are membrane protrusions and provide a valuable comparison to apoptopodia. The researchers also observed the role of PANX1 membrane channels and vesicular trafficking in the regulation of membrane protrusions formed by A431 cells.
Among the findings, researchers discovered that apoptotic membrane protrusion can form without actin Polymerization. In addition, researchers noted that microtubules may play a role in the formation of apoptotic bodies in only apoptotic THP-1 monocytes, but not Jurkat T cells. Researchers observed that apoptotic cell disassembly can occur in the absence of microtubule assembly and actin polymerization. It was found that within Jurkat T cells, vimentin likely has no significant effect on apoptotic disassembly. After examining its effect on apoptotic body formation researchers concluded that the disassembly of apoptotic A431 cells does not involve microtubules. Researchers observed that apoptotic cell disassembly in A431 cells is regulated by PANX1 membrane channels and vesicular trafficking.
While the researchers did note that certain aspects of apoptopodia still need to be further investigated, the overall findings of the study “Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis” by (Caruso et al., 2019) are highly significant. The conclusion and results of this study highly suggest that apoptotic membrane protrusions are in their own class of membrane protrusion. Fig. 1 a. on page 864 depicts the steps of apoptotic cell disassembly in Jurkat T cells and THP-1 monocytes. The three steps are membrane blebbing, formation of protrusions, and cell fragmentation. The methods used this study could be applied to better understand apoptotic processes in cancer cells. This would be helpful because many kinds of cancerous cells exhibit decreased control over apoptosis.
References
Elmore, S. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology, [online] 35(4), pp.495–516. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117903/.
www.nature.com. (2014). Microtubules, Filaments | Learn Science at Scitable. [online] Available at: https://www.nature.com/scitable/topicpage/microtubules-and-filaments-14052932/#:~:text=Microtubules%20are%20the%20largest%20type.
Caruso, S., Atkin-Smith, G.K., Baxter, A.A., Tixeira, R., Jiang, L., Ozkocak, D.C., Santavanond, J.P., Hulett, M.D., Lock, P., Phan, T.K. and Poon, I.K.H. (2019). Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis. Apoptosis, 24(11-12), pp.862–877.