cellular mechanics

Postdoctoral Positions at the University of Pittsburgh in Cellular Mechanics and Biophysics of Morphogenesis

Recent developments in computational cell and biomolecular mechanics have provided valuable insights into the mechanical properties of cells, subcellular components and biomolecules, while simultaneously complementing new experimental techniques used for deciphering the structure–function paradigm in living cells. These computational approaches have direct implications in understanding the state of human health and the progress of disease and can therefore aid immensely in the diagnosis and treatment of diseases.

Dear Colleague,

We want to draw your attention to and encourage your participation in a special session on Multiscale Modeling and Simulation of the thirteenth Pacific Symposium on Biocomputing (PSB), to be held January 4-8, 2008, on the Big Island of Hawaii. PSB is an international, multidisciplinary conference with high impact on the theory and application of computational methods in problems of biological significance. 

The molecular building blocks of a cell include:

This is a model of a single semiflexible polymer chain under sustained tension. The model captures two key features of the cytoskeletal rheology: a) the power-law behavior; and b) the dependence of the power-law on mechanical prestress. The model also reveals the underlying mechanisms.

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.

What might be the differences, if there is any, between mechanical signaling and chemical signaling in a living cell?

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.

Cellular and Molecular Mechanics 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.