Anatomy and Cell Biology

Masataka Kawai, PhD


Professor of Anatomy and Cell Biology

Contact Information

Primary Office: 1-324 Bowen Science Building
51 Newton Road
Iowa City, IA 52242
Phone: 319-335-8101

Web: Publications via PubMed


BA, Science, University of Tokyo, Tokyo, Japan
Physiology Course, Marine Biological Laboratory
PhD, Biology, Princeton University

Post Doctorate, Columbia University

Education/Training Program Affiliations

Department of Anatomy and Cell Biology Graduate Program

Research Summary

Molecular mechanisms of contraction in striated muscles, and the mechanisms of hypertrophic and dilated cardiomyopathy (HCM, DCM).

To study the molecular mechanisms of contraction, it is essential that force can be measured, hence “skinned” single muscle fibers are used, in which the plasma membrane is chemically removed. To learn the function of individual amino acid residues in a contractile protein, it is necessary to replace it with a recombinant protein. We developed a system, in which the thin filament of cardiac fibers is selectively removed by gelsolin, and reconstituted by actin monomers, followed by regulatory proteins tropomyosin (Tpm) and troponin (Tn). Because this procedure does not require any adverse conditions (extreme ionic strength, pH, temperature, etc), the reproducibility of active tension is 104±3%; similarly, the reproducibility of other contractile parameters are excellent. This technique has numerous applications. One can study the actin-myosin interaction without Tpm/Tn; we found that Tpm/Tn increases force/cross-bridge by 50% indicating that the actin-Tpm interaction allosterically activates the actin-myosin interaction. This technique has also been used to study mutant proteins to establish the structure-function relationships. It was further used to learn molecular pathogenesis based on thin filament proteins (actin, Tpm, Tn) that are known to cause HCM and DCM in humans. The technique makes it possible to obtain information on early events of pathogenesis, ie, before complex signaling cascades ensue. In Tpm mutations that cause HCM, we found that tension at pCa 8 increases from 10% (WT) to 30% to cause diastolic problem, whereas in Tpm mutations that cause DCM, tension at pCa 8 and pCa 4.5 both decrease to cause systolic problem.

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Selected Publications

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Bai F, Caster H, Dawson J, Kawai M.  The immediate effect of HCM causing actin mutants E99K and A230V on actin-Tm-myosin interaction in thin-filament reconstituted myocardium.  J Mol Cell Cardiol.  2015 February. 79:123-132.

Wang L, Sadayappan S, Kawai M.  Cardiac Myosin Binding Protein C Phosphorylation Affects Cross-bridge Cycle’s Elementary Steps in a Site-specific Manner.  PLos One.  2014 November 24. 9(11):e113417.

Wang L, Ji X, Barefield D, Sadayappan S, Kawai M.  Phosphorylation of cMyBP-C affects contractile mechanisms in a site specific manner.  Biophys J.  2014. 106:1112-1122.

Bai F, Caster H, Rubenstein P, Dawson J, Kawai M.  Using baculovirus/insect cell expressed recombinant actin to study the molecular pathogenesis of HCM caused by actin mutation A331P.  J Mol Cell Cardiol.  2014. 74:64-75.

Wang L, Kawai M.  A re-interpretation of the rate of tension redevelopment (kTR) in active muscle. .  J Muscle Res Cell Motil.  2013. 34:407-415.

Bai F, Wang L, Kawai M.  A study of tropomyosin’s role in cardiac function and disease using thin-filament reconstituted myocardium.  J Muscle Res Cell Motil.  2013. 34:295-310.

Bai F, Caster H, Pinto J, Kawai M.  Analysis of the molecular pathogenesis of cardiomyopathy-causing cTnT mutants I79N, ΔE96, and ΔK210.  Biophys J.  2013. 104(9):1979-1988.

Wang L, Muthu P, Szczesna-Cordary D, Kawai M.  Characterizations of myosin essential light chain's N-terminal truncation mutant Δ43 in transgenic mouse papillary muscles by using tension transients in response to sinusoidal length alterations.  J Muscle Res Cell Motil.  2013. 34(9):93-105.

Wang L, Muthu P, Szczesna-Cordary D, Kawai M.  Diversity and similarity of motor function and cross-bridge kinetics in papillary muscles of transgenic mice carrying myosin regulatory light chain mutations D166V and R58Q.  J Molec Cell Cardiol.  2013. 62(153-163).

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:(e4741) 1-12.

Date Last Modified: 06/06/2016 - 13:17:48