Vascular smooth muscle contractility depends on cell shape

Abstract

The physiologic role of smooth muscle structure in defining arterial function is poorly understood. We aimed to elucidate the relationship between vascular smooth muscle architecture and functional contractile output. Using microcontact printing and muscular thin film technology, we engineered in vitro vascular tissues with strictly defined geometries and tested their contractile function. In all tissues, vascular smooth muscle cells (VSMCs) were highly aligned with in vivo-like spindle architecture, and contracted physiologically in response to stimulation with endothelin-1. However, tissues wherein the VSMCs were forced into exaggerated spindle elongation exerted significantly greater contraction force per unit cross-sectional area than those with smaller aspect ratios. Moreover, this increased contraction did not occur in conjunction with an increase in traditionally measured contractile phenotype markers. These results suggest that cellular architecture within vascular tissues plays a significant role in conferring tissue function and that, in some systems, traditional phenotype characterization is not sufficient to define a functionally contractile population of VSMCs.

Modulation of macrophage phenotype by cell shape

“…To begin to explore potential molecules that might transduce cell shape into biochemical signals that regulate macrophage polarization, we examined the actin cytoskeleton, which has been implicated in transducing shape in other cell types (11,13,18). Unpatterned, patterned, and cytokine-stimulated macrophages were fixed and stained with phalloidin, and then evaluated by immunofluorescence microscopy.…”

“…Cell shape changes have been associated with different functional states of cells (8), including proliferation and apoptosis (9), nuclear organization (10), stem cell differentiation (11,12), and muscle cell contractility (13). It is thought that interactions between the ECM, cell surface adhesion proteins, and cytoskeleton, as well as subsequent changes in intracellular contractility, are important in mediating shape-induced effects (14).…”

Prediction of Cell Alignment on Cyclically Strained Grooved Substrates

“…For example, experimental studies have demonstrated that, when seeded on substrates having nano/microgrooves, cells tend to orient themselves along the direction of these patterns (8)(9)(10)(11)(12)(13)(14)(15)(16). A similar behavior can be observed when cells are cultured on substrates having linear patterns created with microcontact printing (17)(18)(19)(20), or on top of microposts with an ellipsoidal base (21).…”

An investigation of damage mechanisms in mechanobiological models of in-stent restenosis

“…Finally, both VSMCs and ECs are idealised and represented by circles, despite the fact that ECs are squamous epithelial cells and VSMCs are more spindle like in form, particularly contractile VSMCs [41,42]. VSMC density should be more accurately measured using a 3-D microscopy technique such as confocal microscopy or second harmonic generation microscopy.…”