Avalanches and power law behavior in aortic dissection propagation.
Yu Xunjie,Suki Béla,Zhang Yanhang
Aortic dissection is a devastating cardiovascular disease known for its rapid propagation and high morbidity and mortality. The mechanisms underlying the propagation of aortic dissection are not well understood. Our study reports the discovery of avalanche-like failure of the aorta during dissection propagation that results from the local buildup of strain energy followed by a cascade failure of inhomogeneously distributed interlamellar collagen fibers. An innovative computational model was developed that successfully describes the failure mechanics of dissection propagation. Our study provides the first quantitative agreement between experiment and model prediction of the dissection propagation within the complex extracellular matrix (ECM). Our results may lead to the possibility of predicting such catastrophic events based on microscopic features of the ECM.
Mechanical properties of single cells: Measurement methods and applications.
Hao Yansheng,Cheng Shaokoon,Tanaka Yo,Hosokawa Yoichiroh,Yalikun Yaxiaer,Li Ming
Cell mechanical properties, e.g. elastic and shear modulus, play vital roles in cell activities and functions, such as cell growth, cell division, cell motion, and cell adhesion. Measurement of single-cell mechanical properties has attracted great interest from both academia and industry, due to its importance in a variety of applications, such as cell separation, disease diagnostics, immune status analysis and drug screening. Therefore, accurate, robust and sensitive methods for measuring the mechanical properties of single cells are highly desired. In this review, we classify ten most commonly used methods for measuring single-cell mechanical properties into three main categories based on measurement locations, (1) cell surface (2) cell interior and (3) whole cell, and discuss their utilizations with examples. In addition, we discuss directions for future research, such as improving throughput, automating the probing of cell mechanical properties and integrating different methods to achieve simultaneous measurements of mechanical properties of both cell surface and interior. The above are all necessary to overcome the limitations of current technologies in the mechanical characterization of single cells.
Qualitative analysis of contribution of intracellular skeletal changes to cellular elasticity.
Kwon Sangwoo,Kim Kyung Sook
Cellular and molecular life sciences : CMLS
Cells are dynamic structures that continually generate and sustain mechanical forces within their environments. Cells respond to mechanical forces by changing their shape, moving, and differentiating. These reactions are caused by intracellular skeletal changes, which induce changes in cellular mechanical properties such as stiffness, elasticity, viscoelasticity, and adhesiveness. Interdisciplinary research combining molecular biology with physics and mechanical engineering has been conducted to characterize cellular mechanical properties and understand the fundamental mechanisms of mechanotransduction. In this review, we focus on the role of cytoskeletal proteins in cellular mechanics. The specific role of each cytoskeletal protein, including actin, intermediate filaments, and microtubules, on cellular elasticity is summarized along with the effects of interactions between the fibers.
Revealing the elasticity of an individual aortic fiber during ageing at nanoscale by in situ atomic force microscopy.
Berquand Alexandre,Wahart Amandine,Henry Aubéri,Gorisse Laetitia,Maurice Pascal,Blaise Sébastien,Romier-Crouzet Béatrice,Pietrement Christine,Bennasroune Amar,Sartelet Hervé,Jaisson Stéphane,Gillery Philippe,Martiny Laurent,Touré Fatouma,Duca Laurent,Molinari Michael
Arterial stiffness is a complex process affecting the aortic tree that significantly contributes to cardiovascular diseases (systolic hypertension, coronary artery disease, heart failure or stroke). This process involves a large extracellular matrix remodeling mainly associated with elastin content decrease and collagen content increase. Additionally, various chemical modifications that accumulate with ageing have been shown to affect long-lived assemblies, such as elastic fibers, that could affect their elasticity. To precisely characterize the fiber changes and the evolution of its elasticity with ageing, high resolution and multimodal techniques are needed for precise insight into the behavior of a single fiber and its surrounding medium. In this study, the latest developments in atomic force microscopy and the related nanomechanical modes are used to investigate the evolution and in a near-physiological environment, the morphology and elasticity of aorta cross sections obtained from mice of different ages with an unprecedented resolution. In correlation with more classical approaches such as pulse wave velocity and fluorescence imaging, we demonstrate that the relative Young's moduli of elastic fibers, as well as those of the surrounding areas, significantly increase with ageing. This nanoscale characterization presents a new view on the stiffness process, showing that, besides the elastin and collagen content changes, elasticity is impaired at the molecular level, allowing a deeper understanding of the ageing process. Such nanomechanical AFM measurements of mouse tissue could easily be applied to studies of diseases in which elastic fibers suffer pathologies such as atherosclerosis and diabetes, where the precise quantification of fiber elasticity could better follow the fiber remodeling and predict plaque rupture.
Functional characterization of human coronary artery smooth muscle cells under cyclic mechanical strain in a degradable polyurethane scaffold.
Sharifpoor Soroor,Simmons Craig A,Labow Rosalind S,Paul Santerre J
There are few synthetic elastomeric biomaterials that simultaneously provide the required biological conditioning and the ability to translate biomechanical stimuli to vascular smooth muscle cells (VSMCs). Biomechanical stresses are important physiological elements that regulate VSMC function, and polyurethane elastomers are a class of materials capable of facilitating the translation of stress induced biomechanics. In this study, human coronary artery smooth muscle cells (hCASMCs), which were seeded into a porous degradable polar/hydrophobic/ionic (D-PHI) polyurethane scaffold, were subjected to uniaxial cyclic mechanical strain (CMS) over a span of four weeks using a customized bioreactor. The distribution, proliferation and contractile protein expression of hCASMCs in the scaffold were then analyzed and compared to those grown under static conditions. Four weeks of CMS, applied to the elastomeric scaffold, resulted in statistically greater DNA mass, more cell area coverage and a better distribution of cells deeper within the scaffold construct. Furthermore, CMS samples demonstrated improved tensile mechanical properties following four weeks of culture, suggesting the generation of more extracellular matrix within the polyurethane constructs. The expression of smooth muscle α-actin, calponin and smooth muscle myosin heavy chain and the absence of Ki-67+ cells in both static and CMS cultures, throughout the 4 weeks, suggest that hCASMCs retained their contractile character on these biomaterials. The study highlights the importance of implementing physiologically-relevant biomechanical stimuli in the development of synthetic elastomeric tissue engineering scaffolds.
Haemodynamic and extracellular matrix cues regulate the mechanical phenotype and stiffness of aortic endothelial cells.
Collins Caitlin,Osborne Lukas D,Guilluy Christophe,Chen Zhongming,O'Brien E Tim,Reader John S,Burridge Keith,Superfine Richard,Tzima Ellie
Endothelial cells (ECs) lining blood vessels express many mechanosensors, including platelet endothelial cell adhesion molecule-1 (PECAM-1), that convert mechanical force into biochemical signals. While it is accepted that mechanical stresses and the mechanical properties of ECs regulate vessel health, the relationship between force and biological response remains elusive. Here we show that ECs integrate mechanical forces and extracellular matrix (ECM) cues to modulate their own mechanical properties. We demonstrate that the ECM influences EC response to tension on PECAM-1. ECs adherent on collagen display divergent stiffening and focal adhesion growth compared with ECs on fibronectin. This is because of protein kinase A (PKA)-dependent serine phosphorylation and inactivation of RhoA. PKA signalling regulates focal adhesion dynamics and EC compliance in response to shear stress in vitro and in vivo. Our study identifies an ECM-specific, mechanosensitive signalling pathway that regulates EC compliance and may serve as an atheroprotective mechanism that maintains blood vessel integrity in vivo.