Single molecule measurements of titin elasticity

Titin, with a massive single chain of 3-4 MDa and multiple modular motifs, spans the half-sarcomere of skeletal and cardiac muscles and serves importa nt, multifaceted functions. In recent years, titin has become a favored sub ject of single molecule observations by atomic force microscopy (AFM) and l aser optical trap (LOT). Here we review these single titin molecule extensi on studies with an emphasis on understanding their relevance to titin elast icity in muscle function. Some fundamental aspects of the methods for singl e titin molecule investigations, including the application of dynamic force , the elasticity models for filamentous titin motifs, the technical foundat ions and calibrations of AFM and LOT, and titin sample preparations are pro vided. A chronological review of major publications on recent single titin extension observations is presented. This is followed by summary evaluation s of titin domain folding/unfolding results and of elastic properties of fi lamentous titin motifs. Implications of these single titin measurements for muscle physiology/pathology are discussed and forthcoming advances in sing le titin studies are anticipated. Published by Elsevier Science Ltd.