In a continuing collaboration with NIAMS researchers, atomic force microscopy (AFM) and related bioengineering and physical science methods are being applied to investigate muscle biophysics in relation to physiology and pathologies. We studied the structure and force response properties of Calmodulin, a Ca2+-sensing protein in muscle and brain, and AdhE, a multi-subunit enzyme with functions: acetaldehyde-CoA dehydrogenase, alcohol dehydrogenase, and pyruvate formate lyase (PFL) deactivase. We used advanced AFM imaging and force measurement techniques and carefully studied the effect of the associated immobilization substrate. More extensively, we are working on elastic behaviour of the large muscle proteins such as titin (a massive peptide chain of 3-4 MDa) and nebulin (600-900kDa). We published a comprehensive review of titin research employing AFM, laser optical trap (LOT), and related single molecule technologies, and the resulting understanding on titin biophysical properties. Systematic AFM measurements with extensive data interpretation effort are being focused on understanding the elasticity of the PEVK motif of titin molecule, which has crucial functions of maintaining skeletal and cardiac muscle organization and force responses. Parallel investigations on the nebulin protein are also progressing.
| Wang, K; Forbes, J G; Jin, A J (2001) Single molecule measurements of titin elasticity. Prog Biophys Mol Biol 77:1-44 |
