Insights into the role of elastin in vocal fold health and disease

Abstract

Elastic fibers are large, complex, and surprisingly poorly understood extracellular matrix macromolecules. The elastin fiber, generated from a single human gene--elastin, is a self assembling integral protein that endows critical mechanical proprieties to elastic tissues and organs such as the skin, lungs, and arteries. The biology of elastic fibers is complex because they have multiple components, a tightly regulated developmental deposition, a multistep hierarchical assembly, and unique biomechanical functions. Elastin is present in vocal folds, where it plays a pivotal role in the quality of phonation. This review article provides an overview of the genesis of elastin and its wide-ranging structure and function. Specific distribution within the vocal fold lamina propria across the lifespan in normal and pathological states and its contribution to vocal fold biomechanics will be examined. Elastin and elastin-derived molecules are increasingly investigated for their application in tissue engineering. The properties of various elastin-based materials will be discussed and their current and future applications evaluated. A new level of understanding of the biomechanical properties of vocal fold elastin composites and their molecular basis should lead to new strategies for elastic fiber repair and regeneration in aging and disease.

Figure 1

Schematic of stretching and recoil network of elastin molecules. Elastin molecules are joined via lysyl oxidase cross linking. Each molecule can expand and contract as a random coil thereby the entire elastin molecule can then stretch and recoil as one entity. Adapted from Alberts et al.

Figure 2

Schematic representation of the classical model of elastogenesis. A. Tropoelastin molecules are released into the extracellular space where cross-linking takes place via lysyl oxidase. B. The cross-linked elastin molecules are “chaperoned” to the microfibrillar scaffold site where fiber formation occurs. C. Elastin, together with the microfibrils creates the elastic fiber. Figure reproduced from Mithieux & Weiss.

Figure 3

Elastin Van Gieson stain illustrating elastin fibers (black) in A. Normal rabbit vocal fold/Fibers run parallel to the free edge of the vocal fold and parallel to collagen fibers (pink fibers), and B. Compact and disorganized elastin fibers (black) in a coronal section of a scarred rabbit vocal fold (60 days post injury). 40× magnification for both images. Figure from Thibeault et al., 2002.

Figure 3

Elastin Van Gieson stain illustrating elastin fibers (black) in A. Normal rabbit vocal fold/Fibers run parallel to the free edge of the vocal fold and parallel to collagen fibers (pink fibers), and B. Compact and disorganized elastin fibers (black) in a coronal section of a scarred rabbit vocal fold (60 days post injury). 40× magnification for both images. Figure from Thibeault et al., 2002.