Contractile filament architecture and force transmission in swine airway smooth muscle

Abstract

It is well known that the cyclic interaction of myosin cross bridges with actin filaments is responsible for force and shortening generation in smooth muscle. The intracellular organization of contractile filaments, however, is still poorly understood. Here, we show electron microscopic and functional evidence that contractile filaments in airway smooth muscle lie parallel to the longitudinal axis of the cell bundle, in contrast to the obliquely arranged filaments depicted in conventional models. The parallel arrangement of contractile filaments is maintained despite the fact that individual cells are spindle-shaped. This is accomplished through filament attachment to membrane-associated dense plaques that are in turn connected to similar structures on neighboring cells. Intracellularly, the parallel arrangement is maintained despite the centrally located nucleus. This is accomplished by attachment of actin filaments to the nuclear envelope and making the nucleus a force transmitting structure. The results suggest that smooth muscle cells in tissue form a mechanical syncytium and are able to function properly only as a group.

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

“…The actomyosin cross-bridge is only one of many such structures. Other structures include myosin filaments, actin filaments, cytoskeletal cross-linker molecules, cytosolic dense bodies, membrane adhesion plaques and cell-cell connections [55,185]. There is ample evidence for each of these candidates to be somehow involved in the response to external perturbation [168,174,[186][187][188][189][190][191].…”

“…Nonetheless, key ultrastructural changes are evident when smooth muscle cells are plated as a monolayer in culture dishes, and this underpins a need for careful assessment of the effects of external mechanical strain on myocyte function. In tissues, the contractile apparatus of smooth muscle cells is dotted with a more-or-less regular pattern of dense bodies to which thin filaments are anchored [185,235]. Furthermore, dense plaques, arranged in discrete linear plasma membrane domains between caveolae-rich regions, anchor the contractile apparatus to the cell periphery and serve as junctions between adjacent cells, thereby creating a contractile filament syncytium that is sensitive to externally applied mechanical strain [185,236].…”

“…In tissues, the contractile apparatus of smooth muscle cells is dotted with a more-or-less regular pattern of dense bodies to which thin filaments are anchored [185,235]. Furthermore, dense plaques, arranged in discrete linear plasma membrane domains between caveolae-rich regions, anchor the contractile apparatus to the cell periphery and serve as junctions between adjacent cells, thereby creating a contractile filament syncytium that is sensitive to externally applied mechanical strain [185,236]. In contrast, cultured myocytes characteristically possess multiple, longitudinally oriented cables of actin and myosin called ''stress fibres''.…”

β-Dystroglycan binds caveolin-1 in smooth muscle: a functional role in caveolae distribution and Ca2+ release

“…Mechanisms have evolved to maintain integrity of the contractile apparatus and its association with the membrane and extracellular matrix, so that force can be transmitted between cells, thus preventing plasma membrane damage (Kuo and Seow, 2004;Lapidos et al, 2004). The dystrophin-glycoprotein complex (DGC) provides a strong mechanical link between the intracellular actin cytoskeleton and the extracellular matrix.…”

Mechanotransduction, asthma and airway smooth muscle

“…In smooth muscle cells, the actin and myosin filaments still overlap, but they do not terminate at well-defined z-disks but instead are interconnected at multiple sites -the dense bodies or dense plaques -throughout the cell or the cell membrane, respectively [7,29]. Moreover, the actin and myosin filaments can lengthen, shorten, cross-link with each other, and -together with the dense plaques and dense bodies -they can completely disassemble or re-appear at a different location.…”