Intermediate+Filaments

 Intermediate filaments are fibrous proteins that play vital roles in the shape of a cell, as well as in the function of a cell (Davidson, 2004). There is a broad class of these proteins, and they act as tension-bearing elements that help maintain rigidity in the cell and also anchor several organelles within the cytoplasm (Davidson, 2004). The nuclear lamina is a meshwork array of that line the inner nuclear membrane and governs the shape of the nucleus, and it is composed of intermediate filaments (Davidson, 2004). These filaments are made up of monomers and dimers that become tetramers which form into sheets that are supercoiled into a rope-like bundle (see Figure 1)(Davison, 2004). Some specific intermediate filaments include keratins, found in most animal epithelial cells, and nuclear lamins that constitute the inside of the nuclear membrane (Davidson, 2004).    Figure 1. Formation of intermediate filaments (taken from Davidson, 2004).   Intermediate filaments are important to cellular physiology because these proteins provide the cells with a means of holding their shape and transporting cargo throughout the cell and out of the cell. Microfilaments and microtubules are members of these protein groups, and they bind to other transporting proteins that help the cells move various elements from one side of the cell to the other and also to and from the membranes of the nucleus and the phospholipid bilayer.    The history of intermediate filaments is quite long and well-described, beginning with William T. Astbury in 1932 (Oshima, 2007). Astbury was able to use x-ray diffraction and the crystal structure theory in order to publish the first data of a periodic structure of keratin (Oshima, 2007). Electron microscopes were also invented in 1931, and intermediate filaments were being visualized into the 1960’s without realizing quite what they were (Oshima, 2007). The complex molecular structure of keratin was interpreted using guidance from Linus Pauling’s alpha helix model, which led to the prediction of the alpha helical coiled coil structure by Francis Crick in 1952 (Oshima, 2007). However, interpretation of alpha-keratin was pursued through the 1990’s, and many scientists began investigating the physical and biological aspects of intermediate filaments (Oshima, 2007). Peter Steinert then discovered the polymerization of intermediate filaments form denatured keratin that provided the physical assay for assessing the protein subunit requirements necessary for filament formation (Oshima, 2007).    Current research in the area of intermediate filaments is very broad and has become much more involved. In a research article called “Intermediate filament-deficient cells are mechanically softer at large deformation: A multi-scale simulation study” from July 2010, scientists used a computational model in order to reveal what structural deformations occurred under differing intermediate filament densities (Bertaud et al., 2010). The study found that under applied stress and strain, intermediate filaments were proven to be key contributors to cell stiffness and deformation at large deformation, and also that changes in filament densities result in alterations of the deformation state of the cell nucleus (Bertaud et al., 2010). Another study titled “Inroads into the structure and function of intermediate filament networks” from January 2012 portrayed how intermediate filaments remain the least understood cytoskeletal systems in respects to structure and function (Goldman et al., 2012). The study revealed that intermediate filaments are encoded by a large gene family that is developmentally regulated in a specific fashion by cells and tissues (Goldman et al., 2012). A third research article, called “Dynamics of //in vitro// intermediate filament length distributions” from September 2013 used an aggregation model with explicit expression of association rate constants to study type III intermediate filament length distribution dynamics (Portet, 2013). Four models were created to fit experimental data that led to the identification of the assembly dynamics of rate constants that decreased with respect to filament size when the aggregation involved at least one short filament, showing the flexible nature of filaments and their sizes in the assembly of intermediate filaments (Portet, 2013).   <span style="font-family: "Times New Roman","serif";">References: <span style="font-family: "Times New Roman",Times,serif;"> <span style="font-family: "Times New Roman","serif";">1.) Bertaud, J., Qin, Z., Buehler, M.J. Intermediate filament-deficient cells are mechanically softer at large deformation: A multi-scale simulation study, Acta Biomaterialia, Volume 6, Issue 7, July 2010, Pages 2457-2466. <span style="font-family: "Times New Roman",Times,serif;"> <span style="font-family: "Times New Roman","serif";">2.) Davidson, Michael W. "Intermediate Filaments." //Molecular Expressions//. Florida State University, 14 Dec. 2004. Web. 13 Oct. 2013. <http://micro.magnet.fsu.edu/cells/intermediatefilaments/intermediatefilaments.html>. <span style="font-family: "Times New Roman",Times,serif;"> code <span style="font-family: "Times New Roman","serif"; font-size: 14.66px;">3.)   Goldman, R.D., Cleland, M.M., S.N. Prasanna Murthy, Mahammad, S., Kuczmarski, E.R., Inroads into the structure and function of intermediate filament networks, Journal of Structural Biology, Volume 177, Issue 1, January 2012, Pages 14-23. code <span style="font-family: "Times New Roman",Times,serif;">  code <span style="font-family: "Times New Roman","serif"; font-size: 14.66px;">([]) code <span style="font-family: "Times New Roman",Times,serif;">  <span style="font-family: "Times New Roman","serif";">4.) Oshima, Robert G. "Intermediate Filaments: A Historical Perspective." //National Institutes of Health// 313.10 (2007). Web. 13 Oct. 2013. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1950476/>. <span style="font-family: "Times New Roman",Times,serif;"> <span style="font-family: "Times New Roman","serif";"> ([]) <span style="font-family: "Times New Roman",Times,serif;"> code <span style="font-family: "Times New Roman","serif"; font-size: 14.66px;">5.)   Portet, Stephanie. Dynamics of in vitro intermediate filament length distributions, Journal of Theoretical Biology, Volume 332, 7 September 2013, Pages 20-29.             (http://www.sciencedirect.com/science/article/pii/S0022519313001574 code <span style="font-family: "Times New Roman",Times,serif;">
 * <span style="font-family: "Times New Roman",Times,serif;"> Intermediate Filaments **
 * <span style="font-family: "Times New Roman",Times,serif;"> Research history **
 * <span style="font-family: "Times New Roman",Times,serif;"> Current research **