Bronchospasm and its Biophysical Basis in Airway Smooth Muscle

Airways hyperresponsiveness is a cardinal feature of asthma but remains unexplained. In asthma, the airway smooth muscle cell is the key end-effector of bronchospasm and acute airway narrowing, but in just the past five years our understanding of the relationship of responsiveness to muscle biophysics has dramatically changed. It has become well established, for example, that muscle length is equilibrated dynamically rather than statically, and that non-classical features of muscle biophysics come to the forefront, including unanticipated interactions between the muscle and its time-varying load, as well as the ability of the muscle cell to adapt rapidly to changes in its dynamic microenvironment. These newly discovered phenomena have been described empirically, but a mechanistic basis to explain them is only beginning to emerge

Airway obstruction in asthma: does the response to a deep inspiration matter?

Airway hyperresponsiveness in asthma may not be a problem of too much airway smooth muscle strength. Rather, it may be a problem of too little of the factors that oppose muscle shortening. The weight of available evidence seems to support the idea that loss of the dilating response to a deep inspiration may play a central role in this process, and that the locus of the response is within the airway smooth muscle cell. Bridge dynamics and plastic reorganization of the smooth muscle cytoskeleton are the focus of this commentary; how these factors interact and details about underlying mechanisms remain unclear

Turbulent pseudo-sound production in atherosclerotic arteries.

Massachusetts Institute of Technology. Dept. of Mechanical Engineering. Thesis. 1974. Ph.D.Vita.Bibliography: leaves 114-118.Ph.D

Method and system for measurement of mechanical properties of molecules and cells

Mechanical stresses and deformations are applied directly to cell surface receptors or molecules and measured using a system including a magnetic twisting device in combination with ferromagnetic microbeads coated with ligands for integrins or any other surface receptors. The system can be used diagnostically to characterize cells and molecules and to determine the effect of transformation and compounds, including drugs, on the cells and molecules. The system can also be used to induce cells to grow or alter production of molecules by the cells

Cell Migration Driven by Cooperative Substrate Deformation Patterns

Most eukaryotic cells sense and respond to the mechanical properties of their surroundings. This can strongly influence their collective behavior in embryonic development, tissue function, and wound healing. We use a deformable substrate to measure collective behavior in cell motion due to substrate mediated cell-cell interactions. We quantify spatial and temporal correlations in migration velocity and substrate deformation, and show that cooperative cell-driven patterns of substrate deformation mediate long-distance mechanical coupling between cells and control collective cell migration

Effects of increasing tidal volume and end-expiratory lung volume on induced bronchoconstriction in healthy humans

Background: Increasing functional residual capacity (FRC) or tidal volume (VT) reduces airway resistance and attenuates the response to bronchoconstrictor stimuli in animals and humans. What is unknown is which one of the above mechanisms is more effective in modulating airway caliber and whether their combination yields additive or synergistic effects. To address this question, we investigated the effects of increased FRC and increased VT in attenuating the bronchoconstriction induced by inhaled methacholine (MCh) in healthy humans. Methods: Nineteen healthy volunteers were challenged with a single-dose of MCh and forced oscillation was used to measure inspiratory resistance at 5 and 19 Hz (R5 and R19), their difference (R5-19), and reactance at 5 Hz (X5) during spontaneous breathing and during imposed breathing patterns with increased FRC, or VT, or both. Importantly, in our experimental design we held the product of VT and breathing frequency (BF), i.e, minute ventilation (VE) fixed so as to better isolate the effects of changes in VT alone. Results: Tripling VT from baseline FRC significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Doubling VT while halving BF had insignificant effects. Increasing FRC by either one or two VT significantly attenuated the effects of MCh on R5, R19, R5-19 and X5. Increasing both VT and FRC had additive effects on R5, R19, R5-19 and X5, but the effect of increasing FRC was more consistent than increasing VT thus suggesting larger bronchodilation. When compared at iso-volume, there were no differences among breathing patterns with the exception of when VT was three times larger than during spontaneous breathing. Conclusions: These data show that increasing FRC and VT can attenuate induced bronchoconstriction in healthy humans by additive effects that are mainly related to an increase of mean operational lung volume. We suggest that static stretching as with increasing FRC is more effective than tidal stretching at constant VE, possibly through a combination of effects on airway geometry and airway smooth muscle dynamics.</p

Time-scale and other invariants of integrative mechanical behavior in living cells.

In dealing with systems as complex as the cytoskeleton, we need organizing principles or, short of that, an empirical framework into which these systems fit. We report here unexpected invariants of cytoskeletal behavior that comprise such an empirical framework. We measured elastic and frictional moduli of a variety of cell types over a wide range of time scales and using a variety of biological interventions. In all instances elastic stresses dominated at frequencies below 300 Hz, increased only weakly with frequency, and followed a power law; no characteristic time scale was evident. Frictional stresses paralleled the elastic behavior at frequencies below 10 Hz but approached a Newtonian viscous behavior at higher frequencies. Surprisingly, all data could be collapsed onto master curves, the existence of which implies that elastic and frictional stresses share a common underlying mechanism. Taken together, these findings define an unanticipated integrative framework for studying protein interactions within the complex microenvironment of the cell body, and appear to set limits on what can be predicted about integrated mechanical behavior of the matrix based solely on cytoskeletal constituents considered in isolation. Moreover, these observations are consistent with the hypothesis that the cytoskeleton of the living cell behaves as a soft glassy material, wherein cytoskeletal proteins modulate cell mechanical properties mainly by changing an effective temperature of the cytoskeletal matrix. If so, then the effective temperature becomes an easily quantified determinant of the ability of the cytoskeleton to deform, flow, and reorganize

Monolayer Stress Microscopy: Limitations, Artifacts, and Accuracy of Recovered Intercellular Stresses

In wound healing, tissue growth, and certain cancers, the epithelial or the endothelial monolayer sheet expands. Within the expanding monolayer sheet, migration of the individual cell is strongly guided by physical forces imposed by adjacent cells. This process is called plithotaxis and was discovered using Monolayer Stress Microscopy (MSM). MSM rests upon certain simplifying assumptions, however, concerning boundary conditions, cell material properties and system dimensionality. To assess the validity of these assumptions and to quantify associated errors, here we report new analytical, numerical, and experimental investigations. For several commonly used experimental monolayer systems, the simplifying assumptions used previously lead to errors that are shown to be quite small. Out-of-plane components of displacement and traction fields can be safely neglected, and characteristic features of intercellular stresses that underlie plithotaxis remain largely unaffected. Taken together, these findings validate Monolayer Stress Microscopy within broad but well-defined limits of applicability