Titin elasticity and mechanism of passive force development in rat cardiac myocytes probed by thin-filament extraction

Biophys J. 1997 Oct;73(4):2043-53. doi: 10.1016/S0006-3495(97)78234-1.

Abstract

Titin (also known as connectin) is a giant filamentous protein whose elastic properties greatly contribute to the passive force in muscle. In the sarcomere, the elastic I-band segment of titin may interact with the thin filaments, possibly affecting the molecule's elastic behavior. Indeed, several studies have indicated that interactions between titin and actin occur in vitro and may occur in the sarcomere as well. To explore the properties of titin alone, one must first eliminate the modulating effect of the thin filaments by selectively removing them. In the present work, thin filaments were selectively removed from the cardiac myocyte by using a gelsolin fragment. Partial extraction left behind approximately 100-nm-long thin filaments protruding from the Z-line, whereas the rest of the I-band became devoid of thin filaments, exposing titin. By applying a much more extensive gelsolin treatment, we also removed the remaining short thin filaments near the Z-line. After extraction, the extensibility of titin was studied by using immunoelectron microscopy, and the passive force-sarcomere length relation was determined by using mechanical techniques. Titin's regional extensibility was not detectably affected by partial thin-filament extraction. Passive force, on the other hand, was reduced at sarcomere lengths longer than approximately 2.1 microm, with a 33 +/- 9% reduction at 2.6 microm. After a complete extraction, the slack sarcomere length was reduced to approximately 1.7 microm. The segment of titin near the Z-line, which is otherwise inextensible, collapsed toward the Z-line in sarcomeres shorter than approximately 2.0 microm, but it was extended in sarcomeres longer than approximately 2.3 microm. Passive force became elevated at sarcomere lengths between approximately 1.7 and approximately 2.1 microm, but was reduced at sarcomere lengths of >2.3 microm. These changes can be accounted for by modeling titin as two wormlike chains in series, one of which increases its contour length by recruitment of the titin segment near the Z-line into the elastic pool.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biomechanical Phenomena
  • Biophysical Phenomena
  • Biophysics
  • Cell Fractionation
  • Connectin
  • Elasticity
  • Gelsolin
  • In Vitro Techniques
  • Microscopy, Immunoelectron
  • Models, Cardiovascular
  • Molecular Structure
  • Muscle Proteins / chemistry*
  • Muscle Proteins / physiology*
  • Muscle Proteins / ultrastructure
  • Myocardial Contraction / physiology*
  • Myocardium / chemistry*
  • Myocardium / cytology
  • Myocardium / ultrastructure
  • Protein Kinases / chemistry*
  • Protein Kinases / physiology*
  • Protein Kinases / ultrastructure
  • Rats
  • Sarcomeres / chemistry
  • Sarcomeres / physiology
  • Sarcomeres / ultrastructure

Substances

  • Connectin
  • Gelsolin
  • Muscle Proteins
  • Protein Kinases