title: 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.
authors: Disease Biophysics Group, Harvard Stem Cell Institute, Wyss Institute of Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA.
authors: Patrick W
authors: PW
authors: Alford
authors: Alexander P
authors: AP
authors: Nesmith
authors: Johannes N
authors: JN
authors: Seywerd
authors: Anna
authors: A
authors: Grosberg
authors: Kevin Kit
authors: KK
authors: Parker
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D008841:Actin Cytoskeleton / Q000378:metabolism; D002467:Cell Nucleus / Q000502:physiology; D048430:Cell Shape / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D024745:Smooth Muscle Myosins / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods; D054457:Tissue Scaffolds / Q000737:chemistry; D014471:Umbilical Veins / Q000166:cytology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D003598:Cytoskeletal Proteins; D004129:Dimethylpolysiloxanes; D019332:Endothelin-1; D005353:Fibronectins; D007797:Laminin; D009124:Muscle Proteins; C100762:SMTN protein, human; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D024745:Smooth Muscle Myosins; D018995:Myosin Heavy Chains; C049347:fasudil