Biochemical and biomechanical properties of the pacemaking sinoatrial node extracellular matrix are distinct from contractile left ventricular matrix

Abstract

Extracellular matrix plays a role in differentiation and phenotype development of its resident cells. Although cardiac extracellular matrix from the contractile tissues has been studied and utilized in tissue engineering, extracellular matrix properties of the pacemaking sinoatrial node are largely unknown. In this study, the biomechanical properties and biochemical composition and distribution of extracellular matrix in the sinoatrial node were investigated relative to the left ventricle. Extracellular matrix of the sinoatrial node was found to be overall stiffer than that of the left ventricle and highly heterogeneous with interstitial regions composed of predominantly fibrillar collagens and rich in elastin. The extracellular matrix protein distribution suggests that resident pacemaking cardiomyocytes are enclosed in fibrillar collagens that can withstand greater tensile strength while the surrounding elastin-rich regions may undergo deformation to reduce the mechanical strain in these cells. Moreover, basement membrane-associated adhesion proteins that are ligands for integrins were of low abundance in the sinoatrial node, which may decrease force transduction in the pacemaking cardiomyocytes. In contrast to extracellular matrix of the left ventricle, extracellular matrix of the sinoatrial node may reduce mechanical strain and force transduction in pacemaking cardiomyocytes. These findings provide the criteria for a suitable matrix scaffold for engineering biopacemakers.

Human Atrial Fibroblast Adaptation to Heterogeneities in Substrate Stiffness

“…During the inflammatory phase following myocardial infarction, tissue stiffness in the infarct area is decreased due to collagen degradation and death of cardiomyocytes. This is followed by massive collagen deposition over weeks leading to an increase in tissue stiffness to more than 55 kPa, depending on species, form of fibrosis, and duration of tissue remodeling (Holmes et al, 2005;Berry et al, 2006;Gluck et al, 2017;Farré et al, 2018). In contrast, the elastic modulus of in vitro mouse fibroblast spheroids was determined to be in the range of 0.5-3.5 kPa (Jorgenson et al, 2017).…”

Piezo1 Channels Contribute to the Regulation of Human Atrial Fibroblast Mechanical Properties and Matrix Stiffness Sensing

“…For example, the early inflammatory phase following myocardial infarction is characterized by a softening of the myocardium down to stiffnesses of a few kilopascals [ 3 ], due to collagen degradation and cardiomyocyte death. In contrast, values exceeding 50 kilopascals have been observed in fully mature ventricular scars several months or years after injury [ 4 , 5 , 6 , 7 ]. The current state of knowledge about the sensing of passive mechanics from cell to tissue levels in the heart has been reviewed recently in detail [ 8 ].…”

Evaluation and refinement of sample preparation methods for extracellular matrix proteome coverage

“…These methods typically consist of a decellularization step followed by chaotrope extraction, either alone [15][16][17][18] or followed by dilution and digestion with LysC and/or Trypsin in preparation for LC-MS/MS analysis. [19][20][21][22][23][24][25] Biochemical methods have also been developed which use chemical digestion to solubilize and access highly insoluble ECM proteins of interest. 4,26 We have previously developed methods which utilize chemical digestion with cyanogen bromide (CNBr) 14 and hydroxylamine hydrochloride (HA).…”