Three parallel algorithms for classical molecular dynamics are presented. The first assigns each processor a fixed subset of atoms; the second assigns each a fixed subset of inter-atomic forces to compute; the third assigns each a fixed spatial region. The algorithms are suitable for molecular dynamics models which can be difficult to parallelize efficiently—those with short-range forces where the neighbors of each atom change rapidly. They can be implemented on any distributed-memory parallel machine which allows for message-passing of data between independently executing processors. The algorithms are tested on a standard Lennard-Jones benchmark problem for system sizes ranging from 500 to 100,000,000 atoms on several parallel supercomputers--the nCUBE 2, Intel iPSC/860 and Paragon, and Cray T3D. Comparing the results to the fastest reported vectorized Cray Y-MP and C90 algorithm shows that the current generation of parallel machines is competitive with conventional vector supercomputers even for small problems. For large problems, the spatial algorithm achieves parallel efficiencies of 90% and a 1840-node Intel Paragon performs up to 165 faster than a single Cray C9O processor. Trade-offs between the three algorithms and guidelines for adapting them to more complex molecular dynamics simulations are also discussed.

Fast parallel algorithms for short-range molecular dynamics

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

https://www.seas.upenn.edu/%7Edischer/pdfs/Cell_on_Gel-CELLpaper.pdf

Matrix elasticity directs stem cell lineage specification.

/pdf/self-assembled-monolayers-of-thiolates-on-metals-as-a-form-1neb0hj3k4.pdf

Self-assembled monolayers of thiolates on metals as a form of nanotechnology.

Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.

/pdf/tissue-cells-feel-and-respond-to-the-stiffness-of-their-6dx0rumap6.pdf

Tissue Cells Feel and Respond to the Stiffness of Their Substrate

We describe a three-dimensional magnetic twisting device that is useful in characterizing the mechanical properties of cells. With the use of three pairs of orthogonally aligned coils, oscillatory mechanical torque was applied to magnetic beads about any chosen axis. Frequencies up to 1 kHz could be attained. Cell deformation was measured in response to torque applied via an RGD-coated, surface-bound magnetic bead. In both unpatterned and micropatterned elongated cells on extracellular matrix, the mechanical stiffness transverse to the long axis of the cell was less than half that parallel to the long axis. Elongated cells on poly-L-lysine lost stress fibers and exhibited little mechanical anisotropy; disrupting the actin cytoskeleton or decreasing cytoskeletal tension substantially decreased the anisotropy. These results suggest that mechanical anisotropy originates from intrinsic cytoskeletal tension within the stress fibers. Deformation patterns of the cytoskeleton and the nucleolus were sensitive to loading direction, suggesting anisotropic mechanical signaling. This technology may be useful for elucidating the structural basis of mechanotransduction.

Mechanical anisotropy of adherent cells probed by a three-dimensional magnetic twisting device.

We report here the creep function measured in three cell types, after a variety of interventions, and over three time decades (from 3 ms to 3.2 s). In each case the response conformed to a power law, implying that no distinct molecular relaxation times or time constants could characterize the response. These results add to a growing body of evidence that stands in contrast to widely used viscoelastic models featuring at most a few time constants. We show instead that the ability of the matrix to deform is time-scale invariant and characterized by only one parameter: the power law exponent that controls the transition between solid-like and liquid-like behaviour. Moreover, we validate linearity by comparison of measurements in the time and frequency domains.

/pdf/linearity-and-time-scale-invariance-of-the-creep-function-in-3kdbxxfb1w.pdf

Linearity and time-scale invariance of the creep function in living cells

We quantified the effects of airway wall remodeling upon airway smooth muscle (ASM) shortening. Isolated ASM from sheep was attached to a servo-controller that applied a physiologic load. This load could be altered to reflect specified changes of airway wall geometry, elasticity, parenchymal tethering, transpulmonary pressure (PL), and fluctuations in PL associated with breathing. Starting at a reference length (Lref), ASM was stimulated with acetlycholine and held at constant PL of 4 cm H2O for 2 h. When all compartments were thickened to simulate the asthmatic airway but PL was held fixed, ASM shortened much more than that in the normal airway (to 0.52Lrefversus0.66Lref). Whenbreathingwithdeepinspirations (DIs) was initiated, within the first three DIs the ASM in the normal airway lengthened to 0.84 Lref, whereas that in the asthmatic airway remained stuck at 0.53 Lref. Thickening of the smooth muscle layer alone produced the greatest muscle shortening (to 0.47 Lref) when compared with thickening of only submucosal (to 0.67 Lref) or only adventitial (to 0.62 Lref) compartments. With increased ASM mass, the ASM failed to lengthen in responseto DIs, whereasin the airway with thickened submucosal and adventitial layers ASM lengthened dramatically (to 0.83 Lref). These findings confirm the long-held conclusion that increased muscle mass is the functionally dominant derangement, but mechanisms accountingfor this conclusiondiffer dramatically from those previously presumed. Furthermore, increased ASM mass explained both hyperresponsiveness and the failure of a DI to relax the asthmatic airway.

/pdf/airway-hyperresponsiveness-remodeling-and-smooth-muscle-mass-1w23k0496b.pdf

Airway Hyperresponsiveness, Remodeling, and Smooth Muscle Mass: Right Answer, Wrong Reason?

Prestress mediates force propagation into the nucleus.

Tractions that cells exert on their substrates are essential in cell spreading, migration, and contraction. These tractions can be determined by plating the cells on a flexible gel and measuring the deformation of the gel by using fluorescent beads embedded just below the surface of the gel. In this article we describe the image correlation method (ICM) optimized for determining the displacement field of the gel under a contracting cell. For the calculation of the traction field from the displacement field we use the recently developed method of Fourier transform traction cytometry (FTTC). The ICM and FTTC methods are applied to human airway smooth muscle cells during stimulation with the contractile agonist histamine or the relaxing agonist isoproterenol. The overall intensity of the cell contraction (the median traction magnitude, the energy transferred from the cell to the gel, and the net contractile moment) increased after activation with histamine, and decreased after treatment with isoproterenol. Cells exhibited regional differences in the time course of traction during the treatment. Both temporal evolution and magnitude of traction increase induced by histamine varied markedly among different cell protrusions, whereas the nuclear region showed the smallest response. These results suggest that intracellular mediators of cell adhesion and contraction respond to contractile stimuli with different rates and intensities in different regions of the cell.

/pdf/spatial-and-temporal-traction-response-in-human-airway-3obds2nogj.pdf

James P. Butler

Papers

Mechanical anisotropy of adherent cells probed by a three-dimensional magnetic twisting device.

Linearity and time-scale invariance of the creep function in living cells

Airway Hyperresponsiveness, Remodeling, and Smooth Muscle Mass: Right Answer, Wrong Reason?

Prestress mediates force propagation into the nucleus.

Spatial and temporal traction response in human airway smooth muscle cells.