Effect of mechanical stresses and strains on the biology of skeletal muscle. Force transduction in skeletal muscle across the sarcolemma. Function of integrins in skeletal muscle development. Etiology of muscle contractures and myotendinous pathologies. The primary interest of my laboratory is to study the effects of altered mechanics on the biology of musculoskeletal tissues. Two important biomechanical parameters are: stress and strain. I focus on the effects of strain (stretch) on muscle. To study the effects of stretch on muscle I use a dual approach: 1. An in vivo model of limb lengthening. 2. An in vitro model whereby cultured muscle cells are grown on a flexible membrane. The rabbit model lends itself more for functional (electrophysiological) measurements, and the procedure is similar to the intervention in humans (Ilizarov surgery). The culture model allows investigation of possible mechanisms and exploration of the use of therapeutic agents. In the limb lengthening model, I study the degree of satellite cell/myoblast proliferation, muscle regeneration, fiber phenotype by using immunohistological, biochemical and ultrastructural metods. A second interest of the laboratory is to understand the mechanism of how the contractile force generated in a skeletal muscle fiber is transmitted to the surrounding, noncontractile connective tissue. A potential candidate that can mediate this interaction is a group of molecules, called integrins. Both the in vitro and in vivo model explore these questions. A direct application of this research is to increase our understanding in the etiology, treatment and prevention of muscle contractures, a complication of a number of orthopaedic procedures. Data from these experiments should provide a scientific basis for treatments such as limb lengthening and improve our understanding of certain rehabilitation techniques. It would also broaden our insight of overuse injuries such as myotendinous pathologies.
P.G. Dedeyne, A.O'Neill, W.G. Resneck, G.M. Dymtrenko, D.W. Pumplin, R.J. Bloch. The vitronectin receptor associates with clathrin-coated membrane domains via the cytoplasmic domain of its beta-5 subunit. J. Cell. Science, 111, 2729-2740.