ORIGINAL PAPER Biomechanics of the sarcolemma and costameres in single skeletal muscle fibers from normal and dystrophin-null mice K. P. Garcı ´a-Pelagio • R. J. Bloch • A. Ortega • H. Gonza ´lez-Serratos Received: 26 November 2010 / Accepted: 11 January 2011 / Published online: 11 February 2011 Ó Springer Science+Business Media B.V. 2011 Abstract We studied the biomechanical properties of the sarcolemma and its links through costameres to the con- tractile apparatus in single mammalian myofibers of Extensor digitorum longus muscles isolated from wild (WT) and dystrophin-null (mdx) mice. Suction pressures (P) applied through a pipette to the sarcolemma generated a bleb, the height of which increased with increasing P. Larger increases in P broke the connections between the sarcolemma and myofibrils and eventually caused the sar- colemma to burst. We used the values of P at which these changes occurred to estimate the tensions and stiffness of the system and its individual elements. Tensions of the whole system and the sarcolemma, as well as the maximal tension sustained by the costameres, were all significantly lower (1.8–3.3 fold) in muscles of mdx mice compared to WT. Values of P at which separation and bursting occur- red, as well as the stiffness of the whole system and of the isolated sarcolemma, were *2-fold lower in mdx than in WT. Our results indicate that the absence of dystrophin reduces muscle stiffness, increases sarcolemmal deforma- bility, and compromises the mechanical stability of costa- meres and their connections to nearby myofibrils. Keywords Muscle mechanics  Costamere  mdx  Superficial tension  Dystrophic muscle  Muscular dystrophy Introduction Costameres are structures at the sarcolemma of striated muscle fibers that align circumferentially with the Z disks and the M bands of the nearest myofibrils. Costameres maintain and coordinate the organization of the sarco- lemma with the underlying contractile apparatus, while ensuring that distortions in the sarcolemma during isotonic contractions, that lead to shortening below the equilibrium length, are small and periodic (Bloch et al. 2002; Bloch and Gonzalez-Serratos 2003; Anastasi et al. 2008). They also organize membrane domains at the sarcolemma that are enriched in proteins, signaling molecules, ion channels and pumps, that are essential for proper physiological function of striated muscles (Brenman et al. 1995; Williams and Bloch 1999a; Oak et al. 2003; Ervasti 2003). They con- stitute an essential structure in the pathway for lateral force transmission from myofibrils through the sarcolemma to the extracellular matrix, and ultimately to the tendons (Bloch and Gonzalez-Serratos 2003). Defects in proteins at costameres can compromise muscle force production dur- ing contraction either directly, by reducing the efficiency of lateral force transmission, or indirectly, by increasing the chances that the sarcolemma will be weakened and dam- aged, resulting in degeneration or death of the myofiber (Reed and Bloch 2005; Blaauw et al. 2008). Many mus- cular dystrophies, associated with a profound weakness and fragility of myofibers (Barton 2006), have been linked to alterations in costameric proteins such as dystrophin (Hoffman et al. 1987; Williams and Bloch 1999b; K. P. Garcı ´a-Pelagio  A. Ortega Departamento de Bioquı ´mica, Facultad de Medicina, Universidad Nacional Auto ´noma de Me ´xico, Mexico, DF 04510, Mexico R. J. Bloch  H. Gonza ´lez-Serratos Department of Physiology, University of Maryland, School of Medicine, 655 West Baltimore St., Baltimore, MD 21201, USA H. Gonza ´lez-Serratos (&) Departamento de Fisiologı ´a, Facultad de Medicina, Universidad Nacional Auto ´noma de Me ´xico, Mexico, DF 04510, Mexico e-mail: hgonzale@umaryland.edu 123 J Muscle Res Cell Motil (2011) 31:323–336 DOI 10.1007/s10974-011-9238-9