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

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.

细胞外基质（extracellular matrix）对其驻留细胞的分化与表型发育具有关键调控作用。尽管源自收缩组织的心脏细胞外基质已得到广泛研究并应用于组织工程（tissue engineering）领域，但起搏功能相关的窦房结（sinoatrial node）的细胞外基质特性，目前仍在很大程度上未被阐明。本研究以左心室（left ventricle）为对照，系统探究了窦房结细胞外基质的生物力学特性、生化组成及其分布特征。研究结果显示，窦房结的细胞外基质整体刚度高于左心室，且具有高度异质性：其间质区域主要由纤维状胶原蛋白构成，并富含弹性蛋白（elastin）。细胞外基质的蛋白分布模式提示，驻留的起搏心肌细胞被纤维状胶原蛋白所包裹——这类胶原蛋白可承受更高的抗拉强度，而周围富含弹性蛋白的区域则可发生形变，以降低此类细胞所承受的机械应变。此外，作为整合素（integrins）配体的基底膜相关黏附蛋白，在窦房结中的丰度较低，这可能会削弱起搏心肌细胞的力转导（force transduction）能力。与左心室的细胞外基质不同，窦房结的细胞外基质或可降低起搏心肌细胞所承受的机械应变与力转导水平。上述发现为构建适用于工程化生物起搏器（biopacemakers）的理想基质支架提供了核心依据。