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Emergence of airway smooth muscle mechanical behaviour through dynamic reorganisation of contractile units and force transmission pathways.

J Appl Physiol (1985). 2014 Jan 30;

Authors: Brook BS

Abstract
Airway hyper-responsiveness (AHR) in asthma remains poorly understood despite significant research effort to elucidate relevant underlying mechanisms. In particular, a significant body of experimental work has focussed on the effect of tidal fluctuations on airway smooth muscle (ASM) cells, tissues, lung slices and whole airways in order to understand the bronchodilating effect of tidal breathing and deep inspirations. These studies have motivated conceptual models that involve dynamic reorganisation of both cytoskeletal components as well contractile machinery. In this paper, a biophysical model of the whole ASM cell is presented which combines (i) crossbridge cycling between actin and myosin, (ii) actin-myosin disconnectivity, under imposed length changes, to allow dynamic reconfiguration of “force transmission pathways” and (iii) dynamic parallel-to-serial transitions of contractile units within these pathways, that occur through a length fluctuation. Results of this theoretical model suggest that behaviour characteristic of experimentally observed force-length loops of maximally activated ASM strips can be explained by interactions between the three mechanisms. Crucially, both sustained disconnectivity and parallel-to-serial transitions are necessary to explain the nature of hysteresis and strain-stiffening observed experimentally. The results provide strong evidence that dynamic rearrangement of contractile machinery is a likely mechanism underlying many of the phenomena observed at timescales associated with tidal breathing. This theoretical cell-level model captures many of the salient features of mechanical behaviour observed experimentally and should provide a useful starting block for a bottom-up approach to understanding tissue-level mechanical behaviour.

PMID: 24481961 [PubMed – as supplied by publisher]

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