Mechanisms of aortic carboxypeptidase-like protein secretion and identification of an intracellularly retained variant associated with Ehlers-Danlos syndrome.

Aortic carboxypeptidase-like protein (ACLP) is a collagen-binding extracellular matrix protein that has important roles in wound healing and fibrosis. ACLP contains thrombospondin repeats, a collagen-binding discoidin domain, and a catalytically inactive metallocarboxypeptidase domain. Recently, mutations in the ACLP-encoding gene, AE-binding protein 1 (), have been discovered, leading to the identification of a new variant of Ehlers-Danlos syndrome causing connective tissue disruptions in multiple organs.

On Force and Form: Mechano-Biochemical Regulation of Extracellular Matrix.

The extracellular matrix is well-known for its structural role in supporting cells and tissues, and its important biochemical role in providing signals to cells has increasingly become apparent. These structural and biochemical roles are closely coupled through mechanical forces: the biochemistry of the extracellular matrix determines its mechanical properties, mechanical forces control release or display of biochemical signals from the extracellular matrix, and the mechanical properties of the matrix in turn influence the mechanical set point at which signals are sent. In this Perspective, we explain how the extracellular matrix is regulated by strain and mechanical forces.

Fibronectin fiber creep under constant force loading.

Viscoelasticity is a fundamental property of virtually all biological materials, and proteinaceous, fibrous materials that constitute the extracellular matrix (ECM) are no exception. Viscoelasticity may be particularly important in the ECM since cells can apply mechanical stress resulting from cell contractility over very long periods of time. However, measurements of ECM fiber response to long-term constant force loading are scarce, despite the increasing recognition that mechanical strain regulates the biological function of some ECM fibers.