Anatomy and Cell Biology

Masataka Kawai, PhD

Portrait

Research Associate
Assistant Professor
Associate Research Scientist
Assistant Professor
Associate Professor
Professor
Professor of Anatomy and Cell Biology

Contact Information

Primary Office: 1-324 Bowen Science Building
Iowa City, IA 52242

Email: masataka-kawai@uiowa.edu

Education

BA, Science, University of Tokyo, Tokyo, Japan
Physiology Course, Marine Biological Laboratory, Woods Hole, MA
PhD, Biology, Princeton University, New Jersey

Post Doctoral, Columbia University, New York, New York

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Anatomy and Cell Biology Graduate Program

Research Summary

Molecular mechanisms of contraction are probed using the method called "sinusoidal analysis" in skinned muscle fibers. With this system, force can be measured and the strain (length) sensitivity of the rate constants can be studied. In skinned fibers, the ions and molecules of experimental interest can be perfused into the lattice space, so that both mechanical and chemical perturbations can be applied at the same time. The experimental protocol is to perturb the fiber length during maximal Ca2+ activation, and the concomitant tension transients are recorded. The rate constants of transients are extracted and studied as functions of the ATP, ADP, and phosphate concentrations. From this information, the following crossbridge scheme (see below) consisting of seven states is deduced, together with the 10 kinetic constants that characterize the elementary steps. In this scheme, A=actin, M=myosin, S=ATP, D=ADP, and P=phosphate. With sinusoidal analysis, we investigated the elementary steps in rabbit psoas and soleus fibers, and in ferret and porcine myocardium. Our demonstration of the detailed crossbridge scheme was the first in a muscle fiber system. We also determined force on crossbridges in each state. Our investigations revealed that force is generated at step 4 with the isomerization of the AMDP state, and the same force is maintained with Pi release step 5. Our investigations demonstrated that force is generated as a result of hydrophobic interaction bet-ween the residues of actin and myosin. Future projects include research on substitution of contractile proteins to isoforms or to genetically engineered mutants.

All Publications

Bai F, Wang L, Kawai M.  A study of tropomyosin's role in cardiac function and disease using thin-filament reconstituted myocardium..  Journal of muscle research and cell motility.  2013 May. 
[PubMed]

Bai F, Caster H, Pinto J, Kawai M.  Analysis of the Molecular Pathogenesis of Cardiomyopathy-Causing cTnT Mutants I79N, Î"E96, and Î"K210..  Biophysical journal.  2013 May. 104(9):1979-88.
[PubMed]

Wang L, Muthu P, Szczesna-Cordary D, Kawai M.  Characterizations of myosin essential light chain's N-terminal truncation mutant Î"43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations..  Journal of muscle research and cell motility.  2013 May. 34(2):93-105.
[PubMed]

Bai F, Groth H, Kawai M.  DCM-related tropomyosin mutants E40K/E54K over-inhibit the actomyosin interaction and lead to a decrease in the number of cycling cross-bridges..  PloS one.  2012. 7(10):e47471.
[PubMed]

Bai F, Weis A, Takeda A, Chase P, Kawai M.  Enhanced active cross-bridges during diastole: molecular pathogenesis of tropomyosin's HCM mutations..  Biophysical journal.  2011 February. 100(4):1014-23.
[PubMed]

Russell S, Liu D, Kawai M, Kim Y, Thiel P.  Low-temperature adsorption of H2S on Ag(111)..  The Journal of chemical physics.  2010 September. 133(12):124705.
[PubMed]

Lu X, Heeley D, Smillie L, Kawai M.  The role of tropomyosin isoforms and phosphorylation in force generation in thin-filament reconstituted bovine cardiac muscle fibres..  Journal of muscle research and cell motility.  2010 August. 31(2):93-109.
[PubMed]

Kawai M, Lu X, Hitchcock-Degregori S, Stanton K, Wandling M.  Tropomyosin period 3 is essential for enhancement of isometric tension in thin filament-reconstituted bovine myocardium..  Journal of biophysics (Hindawi Publishing Corporation : Online).  2009. 2009:380967.
[PubMed]

Kawai M, Halvorson H.  Force transients and minimum cross-bridge models in muscular contraction..  Journal of muscle research and cell motility.  2007. 28(41463):371-95.
[PubMed]

Lu X, Tobacman L, Kawai M.  Temperature-dependence of isometric tension and cross-bridge kinetics of cardiac muscle fibers reconstituted with a tropomyosin internal deletion mutant..  Biophysical journal.  2006 December. 91(11):4230-40.
[PubMed]

Kawai M.  Cross-bridge Mechanism in Muscle Contraction .  Tokyo: University of Tokyo Press;  1979.

Date Last Modified: 06/07/2014 - 21:56:23