Nanoscale characterization of the biomechanical properties of collagen fibrils in the sclera

Papi, Massimiliano; Paoletti, Paolo; Geraghty, Brendan; Akhtar, Riaz

doi:10.1063/1.4868388

Cited by 25 publications

(26 citation statements)

References 32 publications

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“…Importantly, these phenotypes in fibronectin-null livers are accompanied by significantly elevated liver matrix stiffness, as determined by AFM, and deteriorated hepatic functions. The novel aspect of our AFM experiments is that we have simultaneously imaged the ultrastructure of the tissue and colocated the mechanical properties, using a novel AFM mechanical mapping method [ 106 ]. We have found that there is approximately a 55% increase in the elastic modulus of fibronectin-null livers compared to controls in vivo (5,128 ± 553.6 MPa in mutant versus 3,313 ± 835.2 MPa in control ( n = 9); P < 0.05; measured at ambient conditions) [ 21 ].…”

Section: Characterization Of Liver Mechanics In Vitro mentioning

confidence: 99%

Molecular Cues Guiding Matrix Stiffness in Liver Fibrosis

Saneyasu

Akhtar

Sakai

2016

BioMed Research International

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Tissue and matrix stiffness affect cell properties during morphogenesis, cell growth, differentiation, and migration and are altered in the tissue remodeling following injury and the pathological progression. However, detailed molecular mechanisms underlying alterations of stiffness in vivo are still poorly understood. Recent engineering technologies have developed powerful techniques to characterize the mechanical properties of cell and matrix at nanoscale levels. Extracellular matrix (ECM) influences mechanical tension and activation of pathogenic signaling during the development of chronic fibrotic diseases. In this short review, we will focus on the present knowledge of the mechanisms of how ECM stiffness is regulated during the development of liver fibrosis and the molecules involved in ECM stiffness as a potential therapeutic target for liver fibrosis.

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Section: Characterization Of Liver Mechanics In Vitro mentioning

confidence: 99%

Molecular Cues Guiding Matrix Stiffness in Liver Fibrosis

Saneyasu

Akhtar

Sakai

2016

BioMed Research International

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“…The spring constant and deflection sensitivity was calibrated using the reference sample, and the same AFM probe was used for imaging every sample. The data were fitted with the Derjaguin-Muller-Toporov model to extract the elastic modulus, as described previously (36). For tissue samples, 10 ϫ 10-m images were collected, and the mean elastic modulus was determined using Bruker Nanoscope software, v 1.5.…”

Section: Methodsmentioning

confidence: 99%

Molecular Mechanism Responsible for Fibronectin-controlled Alterations in Matrix Stiffness in Advanced Chronic Liver Fibrogenesis

Iwasaki

Sakai

Moriya

et al. 2016

Journal of Biological Chemistry

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Fibrosis is characterized by extracellular matrix (ECM) remodeling and stiffening. However, the functional contribution of tissue stiffening to noncancer pathogenesis remains largely unknown. Fibronectin (Fn) is an ECM glycoprotein substantially expressed during tissue repair. Here we show in advanced chronic liver fibrogenesis using a mouse model lacking Fn that, unexpectedly, Fn-null livers lead to more extensive liver cirrhosis, which is accompanied by increased liver matrix stiffness and deteriorated hepatic functions. Furthermore, Fnnull livers exhibit more myofibroblast phenotypes and accumulate highly disorganized/diffuse collagenous ECM networks composed of thinner and significantly increased number of collagen fibrils during advanced chronic liver damage. Mechanistically, mutant livers show elevated local TGF-␤ activity and lysyl oxidase expressions. A significant amount of active lysyl oxidase is released in Fn-null hepatic stellate cells in response to TGF-␤1 through canonical and noncanonical Smad such as PI3 kinase-mediated pathways. TGF-␤1-induced collagen fibril stiffness in Fn-null hepatic stellate cells is significantly higher compared with wild-type cells. Inhibition of lysyl oxidase significantly reduces collagen fibril stiffness, and treatment of Fn recovers collagen fibril stiffness to wild-type levels. Thus, our findings indicate an indispensable role for Fn in chronic liver fibrosis/cirrhosis in negatively regulating TGF-␤ bioavailability, which in turn modulates ECM remodeling and stiffening and consequently preserves adult organ functions. Furthermore, this regulatory mechanism by Fn could be translated for a potential therapeutic target in a broader variety of chronic fibrotic diseases.

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“…PFQNM enables the co-localisation of ultrastructural and mechanical properties with a high resolution. We have previously shown that this technique allows detection of regional variations in the nanomechanical properties of collagen-rich tissue [15] . In this study, we present both nanomechanical and ultrastructural data from the adventitia in a group of patients with known low or high PWV.…”

Section: Introductionmentioning

confidence: 99%