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Molecular Motor-Based Assays for Altered Nanomechanical Function of Ca2+-Regulatory Proteins in Cardiomyopathies

Published online by Cambridge University Press:  01 February 2011

P. Bryant Chase ,
Nicolas M. Brunet ,
Goran Mihajlovic ,
Peng Xiong  and
Stephan von Molnár
P. Bryant Chase
Affiliation:
chase@bio.fsu.edu, Florida State University, Biological Science, Room 222 BIO, 81 Chieftan Way, PO Box 3064370, Tallahassee, FL, 32306-4370, United States, 850-644-0056, 850-644-0481
Nicolas M. Brunet
Affiliation:
brunet@u.washington.edu, Florida State University, Biological Science and Molecular Biophysics, Tallahassee, FL, 32306, United States
Goran Mihajlovic
Affiliation:
mihajlovic@anl.gov, Florida State University, Physics and MARTECH, Tallahassee, FL, 32306, United States
Peng Xiong
Affiliation:
xiong@martech.fsu.edu, Florida State University, Physics and MARTECH, Tallahassee, FL, 32306, United States
Stephan von Molnár
Affiliation:
molnar@martech.fsu.edu, Florida State University, Physics and MARTECH, Tallahassee, FL, 32306, United States
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Abstract

We propose that a thermo-electrical control system for rapid and reversible actuation of biomolecular motors and their partner filaments can also be used to study molecular mechanisms of cardiovascular diseases. We have previously used this device to evaluate the temperature-dependence of unregulated (absence of cardiac Ca2+-regulatory proteins tropomyosin, α-Tm, and troponin, Tn) actin filament sliding powered by myosin motors, which hydrolyze ATP. These assays using the thermo-electric controller can also be applied to regulated thin filaments (F actin plus α-Tm and Tn) to obtain energetic parameters and functional correlates of structural stability at the level of single filaments. This allows us not only to examine Ca2+-dependent sliding of thin filaments, but also to test for altered function of clinically relevant mutations of cardiac myofilament proteins such as those identified in familial hypertrophic cardiomyopathy (FHC).

Keywords

biologicalthermoelectricmicroelectro-mechanical (MEMS)
Type
Research Article
Information
MRS Online Proceedings Library (OPL) , Volume 1096: Symposium FF – Molecular Motors, Nanomachines and Active Nanostructures , 2008 , 1096-FF02-02
Copyright
Copyright © Materials Research Society 2008

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