Tensegrity and mechanoregulation: from skeleton to cytoskeleton

AbstractObjective: To elucidate how mechanical stresses that are applied to the whole organism are transmitted to individual cells and transduced into a biochemical response.Design: In this article, we describe fundamental design principles that are used to stabilize the musculoskeletal system at many different size scales and show that these design features are embodied in one particular form of architecture that is known as tensegrity.Results: Tensegrity structures are characterized by use of continuous tension and local compression; architecture, prestress (internal stress prior to application of external force), and triangulation play the most critical roles in terms of determining their mechanical stability. In living organisms, use of a hierarchy of tensegrity networks both optimizes structural efficiency and provides a mechanism to mechanically couple the parts with the whole: mechanical stresses applied at the macroscale result in structural rearrangements at the cell and molecular level.Conclusion: Due to use of tensegrity architecture, mechanical stress is concentrated and focused on signal transducing molecules that physically associate with cell surface molecules that anchor cells to extracellular matrix, such as integrins, and with load-bearing elements within the internal cytoskeleton and nucleus. Mechanochemical transduction may then proceed through local stress-dependent changes in molecular mechanics, thermodynamics, and kinetics within the cell. In this manner, the entire cellular response to stress may be orchestrated and tuned by altering the prestress in the cell, just as changing muscular tone can alter mechanical stability and structural coordination throughout the whole musculoskeletal system

Towards a Holistic, Yet Gene-Centered Analysis of Gene Expression Profiles: A Case Study of Human Lung Cancers

Genome-wide gene expression profile studies encompass increasingly large number of samples, posing a challenge to their presentation and interpretation without losing the notion that each transcriptome constitutes a complex biological entity. Much like pathologists who visually analyze information-rich histological sections as a whole, we propose here an integrative approach. We use a self-organizing maps -based software, the gene expression dynamics inspector (GEDI) to analyze gene expression profiles of various lung tumors. GEDI allows the comparison of tumor profiles based on direct visual detection of transcriptome patterns. Such intuitive “gestalt” perception promotes the discovery of interesting relationships in the absence of an existing hypothesis. We uncovered qualitative relationships between squamous cell tumors, small-cell tumors, and carcinoid tumor that would have escaped existing algorithmic classifications. These results suggest that GEDI may be a valuable explorative tool that combines global and gene-centered analyses of molecular profiles from large-scale microarray experiments

Outcomes of Midurethral Slings in Women with Concomitant Preoperative Severe Lower Urinary Tract Voiding Symptoms

BACKGROUND: Women with stress urinary incontinence and concomitant obstructive (voiding) lower urinary tract symptoms (LUTS) represent a challenging patient population. Furthermore, their diagnosis and management remain incompletely studied and controversial. We evaluated the outcomes of midurethral sling procedures in women with severe obstructive LUTS. METHODS: We performed a post hoc analysis of women who were part of an institutional review board-approved study of midurethral sling surgery. Preoperatively and at 4-6 weeks postoperatively, patients completed the American Urological Association Symptom Score (AUASS) questionnaire. A postvoid residual urine test was obtained preoperatively, at the time of the voiding trial, and 4-6 weeks postoperatively. Three groups of patients with severe LUTS were then defined: Group A (AUASS \u3e/=20), Group B (voiding subscale \u3e/=12), and Group C (urodynamic obstruction). Patients could be included in more than one group. AUASS was again obtained at a medium-term follow-up of 31.6 months. RESULTS: Of 106 women completing follow-up, 30, 23, and 11 subjects met the criteria for groups A, B, and C, respectively. All had statistically significant improvements in storage and voiding subscales, as well as their stress urinary incontinence. No subject presented with retention or voiding dysfunction at follow-up. These improvements continued at medium-term follow-up with the exception of Group C that failed to demonstrate persistence of statistical improvement in AUASS subscales. CONCLUSION: Patients with stress urinary incontinence and severe voiding LUTS can be treated safely with midurethral sling procedures. In both the short and medium term, these symptoms improve dramatically in the majority of patients

Values of H_0 from Models of the Gravitational Lens 0957+561

The lensed double QSO 0957+561 has a well-measured time delay and hence is useful for a global determination of H0. Uncertainty in the mass distribution of the lens is the largest source of uncertainty in the derived H0. We investigate the range of \hn produced by a set of lens models intended to mimic the full range of astrophysically plausible mass distributions, using as constraints the numerous multiply-imaged sources which have been detected. We obtain the first adequate fit to all the observations, but only if we include effects from the galaxy cluster beyond a constant local magnification and shear. Both the lens galaxy and the surrounding cluster must depart from circular symmetry as well. Lens models which are consistent with observations to 95% CL indicate H0=104^{+31}_{-23}(1-\kthirty) km/s/Mpc. Previous weak lensing measurements constrain the mean mass density within 30" of G1 to be kthirty=0.26+/-0.16 (95% CL), implying H0=77^{+29}_{-24}km/s/Mpc (95% CL). The best-fitting models span the range 65--80 km/s/Mpc. Further observations will shrink the confidence interval for both the mass model and \kthirty. The range of H0 allowed by the full gamut of our lens models is substantially larger than that implied by limiting consideration to simple power law density profiles. We therefore caution against use of simple isothermal or power-law mass models in the derivation of H0 from other time-delay systems. High-S/N imaging of multiple or extended lensed features will greatly reduce the H0 uncertainties when fitting complex models to time-delay lenses.Comment: AASTEX, 48 pages 4 figures, 2 tables. Also available at: http://www.astro.lsa.umich.edu:80/users/philf/www/papers/list.htm

Spherical harmonic decomposition applied to spatial-temporal analysis of human high-density EEG

We demonstrate an application of spherical harmonic decomposition to analysis of the human electroencephalogram (EEG). We implement two methods and discuss issues specific to analysis of hemispherical, irregularly sampled data. Performance of the methods and spatial sampling requirements are quantified using simulated data. The analysis is applied to experimental EEG data, confirming earlier reports of an approximate frequency-wavenumber relationship in some bands.Comment: 12 pages, 8 figures, submitted to Phys. Rev. E, uses APS RevTeX style

Complexity of the Tensegrity Structure for Dynamic Energy and Force Distribution of Cytoskeleton during Cell Spreading

Cytoskeleton plays important roles in intracellular force equilibrium and extracellular force transmission from/to attaching substrate through focal adhesions (FAs). Numerical simulations of intracellular force distribution to describe dynamic cell behaviors are still limited. The tensegrity structure comprises tension-supporting cables and compression-supporting struts that represent the actin filament and microtubule respectively, and has many features consistent with living cells. To simulate the dynamics of intracellular force distribution and total stored energy during cell spreading, the present study employed different complexities of the tensegrity structures by using octahedron tensegrity (OT) and cuboctahedron tensegrity (COT). The spreading was simulated by assigning specific connection nodes for radial displacement and attachment to substrate to form FAs. The traction force on each FA was estimated by summarizing the force carried in sounding cytoskeletal elements. The OT structure consisted of 24 cables and 6 struts and had limitations soon after the beginning of spreading by declining energy stored in struts indicating the abolishment of compression in microtubules. The COT structure, double the amount of cables and struts than the OT structure, provided sufficient spreading area and expressed similar features with documented cell behaviors. The traction force pointed inward on peripheral FAs in the spread out COT structure. The complex structure in COT provided further investigation of various FA number during different spreading stages. Before the middle phase of spreading (half of maximum spreading area), cell attachment with 8 FAs obtained minimized cytoskeletal energy. The maximum number of 12 FAs in the COT structure was required to achieve further spreading. The stored energy in actin filaments increased as cells spread out, while the energy stored in microtubules increased at initial spreading, peaked in middle phase, and then declined as cells reached maximum spreading. The dynamic flows of energy in struts imply that microtubules contribute to structure stabilization

Spatially-resolved spectrophotometric analysis and modelling of the Superantennae

We have performed spatially-resolved spectroscopy of the double-nucleated Ultra-Luminous Infrared Galaxy IRAS 19254-7245, ``the Superantennae'', along the line connecting the two nuclei. These data are analysed with a spectral synthesis code, to derive the star formation and extinction properties of the galaxy. The star formation history (SFH) of the two nuclei is similarly characterized by two different main episodes: a recent burst, responsible of the observed emission lines, and an older one, occurred roughly 1 Gyr ago. We tentatively associate this bimodal SFH with a double encounter in the dynamical history of the merger. We have complemented our study with a detailed analysis of the broad band spectral energy distribution of the Superantennae, built from published photometry, providing the separate optical-to-mm SEDs of the two nuclei. Our analysis shows that: a) the southern nucleus is responsible for about 80% of the total infrared luminosity of the system, b) the L-band luminosity in the southern nucleus is dominated by the emission from an obscured AGN, providing about 40 to 50% of the bolometric flux between 8 and 1000 microns; c) the northern nucleus does not show evidence for AGN emission and appears to be in a post-starburst phase. As for the relative strengths of the AGN and starburst components, we find that, while they are comparable at FIR and sub-mm wavelengths, in the radio the Sy2 emission dominates by an order of magnitude the starburst.Comment: 18 pages. Accepted for publication on A&

Simulations of hydrodynamic interactions among immersed particles in stokes flow using a massively parallel computer

In this paper, a massively parallel implementation of the boundary element method to study particle transport in Stokes flow is discussed. The numerical algorithm couples the quasistatic Stokes equations for the fluid with kinematic and equilibrium equations for the particles. The formation and assembly of the discretized boundary element equations is based on the torus-wrap mapping as opposed to the more traditional row- or column-wrap mappings. The equation set is solved using a block Jacobi iteration method. Results are shown for an example application problem, which requires solving a dense system of 6240 equations more than 1200 times