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Introduction
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January 2006 - August 2010
August 2011 - present
Publications
Publications (40)
Multiple techniques have been developed to isolate contractile smooth muscle cells (SMCs) from tissues with varying degrees of success. However, most of these approaches rely on obtaining fresh tissue, which poses logistical challenges. In the present study, we introduce a novel protocol for isolating contractile SMCs from cryopreserved smooth musc...
Muscle tissue mechanics and contractility measurements have a great advantage over cultured cell level experiments as their mechanical and contractile properties are much closer to in vivo tissue properties. However, tissue level experiments cannot be combined with incubation with the same time resolution and consistency as cell culture studies. He...
Smooth muscle (SM) is found in most hollow organs of the body. Phasic SM, as found in the gut, contracts to propel content, whereas tonic SM, as found in most blood vessels, maintains tension. This force maintenance is referred to as the latch state and occurs at low levels of myosin activation (myosin light chain [LC20] phosphorylation). Molecular...
Objective: This paper presents a force control scheme for brief isotonic holds in an isometrically contracted muscle tissue, with minimal overshoot and settling time to measure its shortening velocity, a key parameter of muscle function. Methods: A two-degree-of-freedom control configuration, formed by a feedback controller and a feedforward contro...
Objective:
This paper presents a force control scheme for brief isotonic holds in an isometrically contracted muscle tissue, with minimal overshoot and settling time to measure its shortening velocity, a key parameter of muscle function.
Methods:
A two-degree-of-freedom control configuration, formed by a feedback controller and a feedforward con...
The increased mass of airway smooth muscle (ASM) in the airways of asthmatic patients may contribute to the pathology of this disease by increasing the capacity for airway narrowing. Evidence for the airway epithelium as a participant in ASM remodeling is accruing. To investigate mechanisms by which airway epithelial cells induce ASM cell (ASMC) pr...
Constriction of airways during asthmatic exacerbation is the result of airway smooth muscle (ASM) contraction. Although it is generally accepted that ASM is hypercontractile in asthma, this has not been unambiguously demonstrated. Whether airway hyperresponsiveness is the result of increased ASM mass alone or also increased contractile force genera...
The in vitro motility assay is a valuable tool to understand motor protein mechanics, but existing algorithms are not optimized for accurate time resolution. We propose an algorithm that combines trace detection with a time-stamped analysis. By tracking filament ends, we minimize data loss from overlapping and crossing filaments. A movement trace f...
Cystic fibrosis (CF) is an autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator gene. Many patients with CF have asthma-like symptoms and airway hyperresponsiveness, which are potentially associated with altered airway smooth muscle(ASM) contractility. Our goal in this study was to assess the contractility o...
In vitro motility assays are a valuable tool in understanding and characterizing motor protein mechanics, but existing algorithms are not optimized for time resolved analyses. We propose an algorithm that combines trace detection with time resolved analysis. By tracking filament ends, we double the number of data points and minimize data loss from...
Rationale:
Isolated human airway smooth muscle (ASM) tissue contractility studies are essential for understanding the role of ASM in respiratory disease, but limited availability and cost render storage options necessary for optimal use. However, to date no comprehensive study of cryopreservation protocols for isolated ASM has been performed.
Met...
Airway smooth muscle (ASM) cells are phenotypically regulated to exist in either a proliferative or a contractile state. However the influence of other airway structural cell types on ASM cell phenotype is largely unknown. Although epithelial cells are known to drive ASM proliferation, their effects on the contractile phenotype are uncertain. In th...
Airway smooth muscle (ASM) orientation and morphology determine the ability of the muscle to constrict the airway. In asthma, ASM mass is increased, but it is unknown whether ASM orientation and morphology are altered as well, or whether the remodelling at the source of the mass increase is ongoing. We dissected human airway trees from asthmatic an...
Background:
Heaves is a naturally occurring equine disease that shares many similarities with human asthma including reversible antigen-induced bronchoconstriction, airway inflammation and remodeling.
Objective:
The purpose of this study was to determine whether the trachealis muscle is mechanically representative of the peripheral airway smooth...
Rationale:
Airway smooth muscle (ASM) plays a key role in airway hyperresponsiveness (AHR) but it is unclear whether its contractility is intrinsically changed in asthma.
Objectives:
To investigate whether key parameters of ASM contractility are altered in subjects with asthma.
Methods:
Human trachea and main bronchi were dissected free of epi...
Rationale: The latch-state describes the ability of tonic smooth muscle to maintain force at reduced ATP consumption and crossbridge cycling rate. In animal models this is evidenced by reduced unloaded shortening velocity (Vmax), presumably indicative of crossbridge cycling rate, and reduced myosin light chain phosphorylation (pMLC). In this study...
While structural changes have been observed in asthmatic airways for more than a century, the importance of airway remodeling did not come into view as a key player in asthma until recently. Its significance can be derived from the fact that supramaximal doses of histamine are not capable of causing full airway constriction in healthy subjects, ind...
Background:
Smooth muscle has the distinctive ability to maintain force for long periods of time and at low energy costs. While it is generally agreed that this property, called the latch-state, is due to the dephosphorylation of myosin while attached to actin, dephosphorylated-detached myosin can also attach to actin and may contribute to force m...
Smooth muscle is unique in its capability to maintain force for long periods of time at low ATP (energy) consumption. This property, called the latch-state, is hypothesized to occur due to the dephosphorylation of myosin while attached to actin. Alternative theories have proposed that dephosphorylated-detached myosin can also re-attach to actin and...
It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a...
Length adaptation in airway smooth muscle (ASM) is attributed to reorganization of the cytoskeleton, and in particular the contractile elements. However, a constantly changing lung volume with tidal breathing (hence changing ASM length) is likely to restrict full adaptation of ASM for force generation. There is likely to be continuous length adapta...
Airway hyperresponsiveness and obstruction are the major characteristics of asthma. Current asthma treatments using antiinflammatory agents and airway smooth muscle (ASM) relaxants are expensive, variable in effectiveness and are associated with several cardiovascular side effects. ASM behaviour in vitro has been studied by various researchers to p...
We present a systematic quantitative analysis of power-law force relaxation and investigate logarithmic superposition of force response in relaxed porcine airway smooth muscle (ASM) strips in vitro. The term logarithmic superposition describes linear superposition on a logarithmic scale, which is equivalent to multiplication on a linear scale. Addi...
Airway smooth muscle contraction is the main driving mechanism in asthma. However, in the dynamic environment of the ASM passive dynamics play an important role. The main aim of this research is to investigate the relative contribution of passive dynamics to ASM tissue dynamics and to characterize this behavior. The major finding of this study is t...
Understanding pressure wave propagation in the lung is of importance for a number of medical devices including those for diagnostics and treatments. The main objective of this research is to quantify the transmitability of the airway tree with respect to pressure oscillations. Ovine lungs are casted to produce a hollow airway tree. Variable pressur...
Current asthma treatments using anti-inflammatory agents and airway smooth muscle (ASM) relaxants are expensive, variable in effectiveness and are associated with several cardiovascular side effects. Previous in vitro experiments conducted on ASM tissues suggest that oscillations applied to contracted muscle result in a reduction in the contractile...
The main driving mechanism in asthmatic attacks is the contraction of airway smooth muscle (ASM). Physiological loading of
ASM by normal breathing and deep inspiration has been shown to reduce ASM contractile force. Our research aims to develop
a mathematical model to describe the dynamic behavior of ASM. The current research focuses on a series of...
The main driving mechanism in asthmatic attacks is the contraction of airway smooth muscle (ASM). Physiological loading of ASM by normal breathing and deep inspiration has been shown to reduce ASM contractile force. Our research involves the development of a mathematical model to describe the dynamic behavior of ASM. In this model length adaptation...
Many respiratory devices are used to help patients to overcome breathing difficulties. As a first step, these equipments are normally tested and calibrated using a lung simulator. Many of the available positive pressure lung simulators achieve the purpose of simulation; however, they neither resemble actual lung vacuum conditions nor can be used fo...
Many respiratory devices are used to help patients to overcome breathing difficulties. As a first step, these equipments are normally tested and calibrated using a lung simulator. Many of the available positive pressure lung simulators achieve the purpose of simulation; however, they neither resemble actual lung vacuum conditions nor can be used fo...
The current study aims to investigate the relative contributions of each of the processes that govern airway smooth muscle mechanical behaviour. Studies have shown that breathing dynamics have a substantial effect on airway constriction in healthy and diseased subjects, yet little is known about the dynamic response of the main instigator of airway...