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.
This is a paper that has been accepted for publication in the Journal of the Mechanics and Physics of Solids from our group. The paper describes the combined effect of material inertia and inhomogeneous material property variation on spontaneous cohesive-crack propagation in functionally graded materials. The preprint is attached as a PDF.
Abstract- The effects of combining functionally graded materials of different inhomogeneous property gradients on the mode-3 propagation characteristics of an interfacial crack are numerically investigated. Spontaneous interfacial crack propagation simulations were performed using the newly developed spectral scheme. The numerical scheme derived and implemented in the present work can efficiently simulate planar crack propagation along functionally graded bimaterial interfaces. The material property inhomogeneity was assumed to be in the direction normal to the interface. Various bimaterial combinations were simulated by varying the material property inhomogeneity length scale. Our parametric study showed that the inclusion of a softening type functionally graded material in the bimaterial system leads to a reduction in the fracture resistance indicated by the increase in crack propagation velocity and power absorbed. An opposite trend of increased fracture resistance was predicted when a hardening material was included in the bimaterial system. The cohesive tractions and crack opening displacements were altered due to the material property inhomogeneity, but the stresses ahead of the cohesive zone remained unaffected.
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.
Recent comments by AA Spector are interesting and deserve further discussion. Earlier elegant work by Maniotis and Ingber demonstrated the interconnectedness between the cell surface (via integrins) and the nucleus through the cytoskeleton. Coffey also promoted the importance of cytoskeleton in mechanical signal transduction in normal cells and the differences in tumor cells. There ideas are not well received, however, by the field. An important issue is the magnitude of the surface deformation: if it is large, then one expects the nucleus to be deformed. A finite element analysis by SM Mijailovich et al (J Appl Physiol, 2003) showed that a localized surface load decays rapidly in space-as a function of distance squared, suggesting that a physiologic load may not be able to deform structures inside the nucleus directly. This is consistent with St Venant principle that states a local force causes only a local deformation. A recent review by Vogel and Sheetz also highlighted the importance of local deformation leading to local biochemical activities.
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.
Listed below is a recent publication of mine in Science for your possible interest and critics. This is a review article focusing on the multiscale simulation issues in strucutral composites. I will be more than happy to discuss with those of you who are interested. The following is the abstract.
The difficult challenge of simulating diffuse and complex fracture patterns in tough structural composites is at last beginning to yield to conceptual and computational advances in fracture modeling. Contributing successes include the refinement of cohesive models of fracture and the formulation of hybrid stress-strain and traction-displacement models that combine continuum (spatially averaged) and discrete damage representations in a single calculation. Emerging hierarchical formulations add the potential of tracing the damage mechanisms down through all scales to the atomic. As the models near the fidelity required for their use as virtual experiments, opportunities arise for reducing the number of costly tests needed to certify safety and extending the design space to include material configurations that are too complex to certify by purely empirical methods.
I am at Boston for MRS 2006 Fall meeting this week, where I met a real "spiderman" at the poster session tonight. I'd like to share with you the following videos which were posted at YouTube by the "spiderman" himself, Mr. Jose Berengueres at Tokyo Instititute of Technology.
Mr. "Spiderman" also has posted a video on fasting climbing robot.
A variable core model of a moving crystal dislocation is proposed and used to derive an expression for the Peierls stress. The dislocation width varies periodically as a dislocation moves through the lattice, which leads to an expression for the Peierls stress in terms of the difference of the total energies in the crystal corresponding to stable and unstable equilibrium configurations of the dislocation, rather than the difference in the misfit energies alone. Results for both edge and mixed dislocations are given and proposed to be used in conjunction with ab initio calculations.
Mechanics of Solids and Materials intends to provide a modern and integrated treatment of the foundations of solid mechanics as applied to the mathematical description of material behavior. The book blends both innovative (e.g., large strain, strain rate, temperature, time-dependent deformation and localized plastic deformation in crystalline solids, and deformation of biological networks) and traditional topics (e.g., elastic theory of torsion, elastic beam and plate theories, and contact mechanics) in a coherent theoretical framework. This, and the extensive use of transform methods to generate solutions, makes the book of interest to structural, mechanical, and aerospace engineers.
The German Academic Exchange Service (DAAD) - in cooperation with science organizations in North America and Germany— is to invite undergraduate students from the US and Canada in the fields of biology, chemistry, physics, earth Sciences and engineering to apply for a summer research internship in Germany. RISE summer placements take place with research groups at universities and top research institutions across Germany. The RISE interns are matched with a doctoral student whom they assist and who will also serve as their mentor. This program is funded by the Federal Ministry of Economics and Technology as part of the European Recovery Program (ERP).
More details at http://www.daad.de/rise/en/1.html.
