biomechanics

Robust biomechanical models are essential for studying the nuclear mechanics and can help shed light on the underlying mechanisms of stress transition in nuclear elements. Here, we develop a computational model for an isolated nucleus undergoing micropipette aspiration. Our model includes distinct components representing the nucleoplasm and the nuclear envelope. The nuclear envelope itself comprises three layers: inner and outer nuclear membranes and one thicker layer representing the nuclear lamina.

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.

We know - or believe - protein function is determined by structure. Crystallographic and NMR studies can provide protein structures with atomic-level details at equilibrium. MD simulations can follow protein conformational changes in time with fs temporal resolution in the absence or presence of a bias mechanism, e.g., applied force, used to induce such changes.

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?

In a recent article in Physical Review Letters, Alain Goriely and Sébastien Neukirch offer a mechanical model of how the free tip of a twining plant can hold onto a smooth support, allowing the plant to grow upward. The model also explains why these vines cannot grow on supports of too large a diameter. Read more.

The mechanics involves large deflection and bifurcation of a rod. I hope to hear opinions from people who know about the mechanics of plants.

Biomechanics is a reasonably well-developed field of study, with a modern history usually linked to the pioneering work of Prof. Y.C. Fung in the 1960s. There are a number of dedicated biomechanics journals (including but not limited to the Journal of Biomechanics and the Journal of Biomechanical Engineering). The field is well-enough established to have several generations of researchers working on the subject at universities across the world.

Symposium DD at the upcoming Materials Research Society Annual Meeting (Nov. 26-Dec. 1, Boston, MA) will be the latest in a series of MRS symposia on the mechanics of biological materials and materials designed following natural principles ("biomimetic" or "bio-inspired").   The full program is available at the MRS website (www.mrs.org).  This topic was also the subject of the August, 2006 focus issue of the Journal of Materials Research, which contained over 30 articles on the subject.

A viscous-elastic-plastic indentation model was used to assess the local variability of properties in healing porcine bone. Constant loading- and unloading-rate depth-sensing indentation tests were performed and properties were computed from nonlinear curve-fits of the unloading displacement-time data. Three properties were obtained from the fit: modulus (the coefficient of an elastic reversible process), hardness (the coefficient of a nonreversible, time-independent process) and viscosity (the coefficient of a nonreversible, time-dependent process). The region adjacent to the dental implant interface demonstrated a slightly depressed elastic modulus along with an increase in local time-dependence (lower viscosity); there was no clear trend in bone hardness with respect to the implant interface.

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.