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Journal Club September 2010: Modeling the Mechanics of Cellular Membranes

Constitutive relations, 2-D vs. 3-D. The starting point for modeling cellular membranes is the constitutive relations in 2-D space. It is important to set up the corresponding equations directly in two dimensions rather than to consider them as an asymptotic limit of three-dimensional relationships, like it is done in the shell theory. The main reason for the direct 2-D relations is that 3-D continuum approaches are not applicable to membranes whose thickness in on the order of magnitude of the dimension of a single molecule.

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Recently I received a message from the Cambridge University Press regarding a coming text on biomechanics entitled Introductory Biomechanics, From Cells to Organisms. by C. Ross Ethier and Craig A. Simmonds. I ordered an exam copy, went through, and found it very interesting. It covers cellular biomechanics, hemodynamics, circulatory system, ocular biomechanics, muscles and movement, and skeletal biomechanics. Each section has a significant number of problems. I examined closely the part on cellular biomechanics which is one of the main areas of my research and teaching interests, and enjoyed reading it. The cellular mechanics is presented in its interrelation to cell structure and biology (there are nice images of cells and their components to use for teaching). The main techniques of probing the cell, such as micropipette aspiration, AFM, optical tweezers, and magnetic cytometry, are considered. Models of the cytoskeleton (tensergity, foams) are also introduced. The math is limited to linear equations, one-dimensional or axisymmetric problems, but it seems appropriate for the introductory level. In addition, some results of computational (finite element) modeling are also included. I certainly expect that this textbook will be quite useful in my teaching. The web site has more details on the book.

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Magnetic Twisting Cytometry and Cell Mechanical Propertries

Some time ago (12-19-06), Daniel Isabey posted an interesting comment on mechanical responses of cells obtained via magnetic twisting cytometry. While the comment was about the nonlinearity of the bead angular displacement, a broader question is how adequately the bead moment/angle relationship represents the complex cell mechanics. There are different patterns of actin bundles at the whole-cell level.

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Back to the Mechanics vs. Biochemistry in Cellular Mechanotransduction

In his interesting response to our comment posted on 11/28, Ning Wang focused on the transmission of a local force generated at the adhesion site(s). We agree that this is a question important to our understanding of the signaling to the nucleus. The question is not only about the range of the force transmission but also about the magnitude of such force because the nucleus is several times stiffer than the cytoskeleton.

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Mechanics vs. Biochemistry in Adhesions-Cytoskeleton-Nucleus Signal Transduction in Cells

The essence of mechanobiology is, probably, the interrelation between mechanical and biochemical factors.  An exciting example of such phenomenon is signaling associated with the interaction between the cell and extracellular matrix (EM).  While some purely biochemical pathways initiated in the area of contact of the cell and EM are known, there are interesting ideas how the mechanical forces, stresses and strains can be involved too. This view goes back to works of Donald Ingber's group in the 90s that showed how perturbations of the adhesion area as a whole and of an individual integrin result in deformation of the cell nucleus. Interestingly, a distinguished oncologist at Johns Hopkins, Donald Coffey, published similar experimental results about the same time, and he also demonstrated that the observed cytoskeleton/nucleus interaction is different in tumor cells. There are several separate pieces of the puzzle that have been resolved: mechanical forces are generated at focal adhesions, the cytoskeleton is involved, nucleus deforms, gene expression changes as a result of perturbation of the adhesions, however, the whole picture of the interrelated mechanical and biochemical factors has yet to be understood. We recently published some results on this topic in the Journal of Biomechanical Engineering (Jean et al., 2004 and 2005). I was glad to find an interest in the same problem from some participants of this website (e.g., N. Wang, Z. Suo,   Long-distance propagation of forces in a cell, 2005 and P.R. LeDuc and R.M. Bellin, Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior, 2006). This aspect of mechanotransduction is important for many areas beyond mechanics such as cancer, wound healing, cell adhesion and motility, effect of surface micro- and nanopatterning, etc.

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