A new journal dedicated to the field of Molecular and Cellular Biomechanics has been formed for about a year. Many members in this community (such as Ning Wang, Cheng Zhu, Phil LeDuc) are on the board of editors. You may want to check it out....
This is a paper by Jizhong Lou and myself, which is in press in Biophysical Journal.
Abstract. Catch bonds, whose lifetimes are prolonged by force, have been observed in selectin-ligand interactions and other systems. Several biophysical models have been proposed to explain this counter-intuitive phenomenon, but none was based on the structure of the interacting molecules and the noncovalent interactions at the binding interface. Here we used molecular dynamics simulations to study changes in structure and atomic-level interactions during forced unbinding of P-selectin from P-selectin glycoprotein ligand-1. A mechanistic model for catch bonds was developed based on these observations. In the model, "catch" results from forced opening of an interdomain hinge that tilts the binding interface to allow two sides of the contact to slide against each other. Sliding promotes formation of new interactions and even rebinding to the original state, thereby slowing dissociation and prolonging bond lifetimes. Properties of this sliding-rebinding mechanism were explored using a pseudo-atom representation and Monte Carlo simulations. The model has been supported by its ability to fit experimental data and can be related to previously proposed two-pathway models.
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.
Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of his immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function.
I was invited by Dr. Zhigang Suo to write a short piece on “Cellular and Molecular Mechanics”. I am writing this informally to introduce this subject matter rather than talk in vernacular such as mechanotransduction, phosphorylation, etc. I have more formal papers if someone is interested in more detailed discussions on this subject area. This is a field in which I have been working for over a decade now and I find it more exciting every day. The question always is how does mechanics affect biological processes. This is a very interdisciplinary subject matter as mechanists, engineers, physicists, chemists, and biologists have been investigating this process from various perspectives. I am obviously not the first to study this process. For most of us, it is realized from an empirical perspective that mechanics matters to biology, but exactly how mechanics specifically alters biochemistry continues to be highly debated today. Mechanics of course matters in many physiological areas. Your blood flows, your heart pumps, your bone and muscle feel mechanics. Not only does the body experience mechanical stimulation, but it reacts biochemically to it. A wonderful example is when people go into space (NASA) for long periods of time. The bone in one’s body begins to resorb in a similar response mode to what one experiences in aging (osteoporosis). This is primarily due to just the change in the gravity (mechanics). Other diseases are related to these issues including the two biggest killers: heart disease and cancer. While biomechanics on this scale has been studied for awhile (Leonardo Da Vinci, who was interested in mechanics, also wrote one of the first texts on anatomy), the movement to the cellular and molecular scales has brought a tremendous amount of excitement. I consider the cell as one of the ultimate smart materials exhibiting these characteristics. The cell has evolved over millions of years and is designed better than almost any system that we can personally build. Just as the biological eye provides a beautiful template for optics based lenses, much can be learned about building technology (“nanotechnology” and “microtechnology”) through examining the behavior of cells and molecules.
