Influences of Desmin and Keratin 19 on Passive Biomechanical Properties of Mouse Skeletal Muscle

Sameer B Shah,Richard M Lovering,Robert J Bloch,Andrea O'Neill,James M Love

doi:10.1155/2012/704061

Abstract

In skeletal muscle fibers, forces must be transmitted between the plasma membrane and the intracellular contractile lattice, and within this lattice between adjacent myofibrils. Based on their prevalence, biomechanical properties and localization, desmin and keratin intermediate filaments (IFs) are likely to participate in structural connectivity and force transmission. We examined the passive load-bearing response of single fibers from the extensor digitorum longus (EDL) muscles of young (3 months) and aged (10 months) wild-type, desmin-null, K19-null, and desmin/K19 double-null mice. Though fibers are more compliant in all mutant genotypes compared to wild-type, the structural response of each genotype is distinct, suggesting multiple mechanisms by which desmin and keratin influence the biomechanical properties of myofibers. This work provides additional insight into the influences of IFs on structure-function relationships in skeletal muscle. It may also have implications for understanding the progression of desminopathies and other IF-related myopathies.

Highlights

Lateral force transmission, both across the sarcolemma and within a single myofiber, is believed to be an important component of the biomechanical function of muscle [1,2,3,4]
We examined the response of extensor digitorum longus (EDL) fibers harvested from 10-month-old wild-type, desmin-null, Keratin 19 (K19)-null, and desmin/K19 double-null mice to tensile loading to examine the relative contributions of each intermediate filament to fiber passive mechanical properties
Post hoc comparison of the quadratic coefficients revealed that wild-type fibers were significantly stiffer than desmin-null (P < 0.002), K19-null (P < 0.006), and double-null (P < 0.002) fibers (Figure 1(b))

Summary

Introduction

Lateral force transmission, both across the sarcolemma and within a single myofiber, is believed to be an important component of the biomechanical function of muscle [1,2,3,4]. Forces must be transmitted both between the plasma membrane and the intracellular myofibrillar lattice, and within this lattice, from myofibril to myofibril. Based on their prevalence, biomechanical properties and localization, intermediate filaments (IFs) are strong candidates to regulate such lateral transmission. IFs composed of desmin and keratins 8 and 19 have been identified as key components of mature skeletal muscle [5,6,7]. Considerable evidence links these IFs to roles in structural connectivity and mechanical function. There are discrepancies regarding the susceptibility of desmin-null muscles to injury, these may be attributable to differences in the strains of desmin-null mice probed, the identity of muscles tested, or injury protocols imposed [17, 18]

Methods

Results

Discussion

Conclusion